diff --git a/Lib/pdb.py b/Lib/pdb.py
index 01451f0229cacb..ee077119a03e0d 100644
--- a/Lib/pdb.py
+++ b/Lib/pdb.py
@@ -374,16 +374,34 @@ def get_default_backend():
     return _default_backend
 
 
-def _pyrepl_available():
-    """return whether pdb should use _pyrepl for input"""
+def _pyrepl_available(stdin=None, stdout=None):
+    """Return whether pdb should use _pyrepl for input.
+
+    stdin and stdout default to sys.stdin and sys.stdout.  Callers that pass
+    explicit streams (such as Pdb) should pass the streams they will use.
+    """
     if os.getenv("PYTHON_BASIC_REPL"):
-        CAN_USE_PYREPL = False
-    else:
-        try:
-            from _pyrepl.main import CAN_USE_PYREPL
-        except ModuleNotFoundError:
-            CAN_USE_PYREPL = False
-    return CAN_USE_PYREPL
+        return False
+    try:
+        from _pyrepl.main import CAN_USE_PYREPL
+    except ModuleNotFoundError:
+        return False
+    if not CAN_USE_PYREPL:
+        return False
+    if stdin is None:
+        stdin = sys.stdin
+    if stdout is None:
+        stdout = sys.stdout
+    # CAN_USE_PYREPL is fixed at import time; streams may no longer be usable
+    # when this is called (e.g. in regrtest worker subprocesses).  Doctests
+    # may replace sys.stdin with a fake object that has no fileno().
+    try:
+        if not os.isatty(stdin.fileno()):
+            return False
+        stdout.fileno()
+        return True
+    except (AttributeError, ValueError, OSError):
+        return False
 
 
 class PdbPyReplInput:
@@ -520,7 +538,7 @@ def __init__(self, completekey='tab', stdin=None, stdout=None, skip=None,
             pass
 
         self.pyrepl_input = None
-        if _pyrepl_available():
+        if _pyrepl_available(self.stdin, self.stdout):
             try:
                 self.pyrepl_input = PdbPyReplInput(self, self.stdin, self.stdout, self.prompt)
             except Exception:
diff --git a/Lib/test/test_pdb.py b/Lib/test/test_pdb.py
index 410f1436ed4d20..88d2218316e593 100644
--- a/Lib/test/test_pdb.py
+++ b/Lib/test/test_pdb.py
@@ -25,7 +25,7 @@
 from test.support.import_helper import import_module
 from test.support.pty_helper import run_pty, FakeInput
 from test.support.script_helper import kill_python
-from unittest.mock import patch
+from unittest.mock import Mock, patch
 
 SKIP_CORO_TESTS = False
 
@@ -4775,14 +4775,27 @@ def foo(self):
         self.assertIn("The specified object 'C.foo' is not a function", stdout)
 
     def test_pyrepl_available(self):
+        tty_stdin = Mock()
+        tty_stdin.fileno.return_value = 0
+        tty_stdout = Mock()
+        tty_stdout.fileno.return_value = 1
+
         with patch.dict(os.environ, {"PYTHON_BASIC_REPL": "1"}):
-            self.assertFalse(pdb._pyrepl_available())
+            self.assertFalse(pdb._pyrepl_available(tty_stdin, tty_stdout))
+
+        with patch.dict(os.environ, {}, clear=True):
+            mod = types.ModuleType("_pyrepl.main")
+            mod.CAN_USE_PYREPL = True
+            with patch.dict("sys.modules", {"_pyrepl.main": mod}), \
+                 patch.object(os, "isatty", return_value=True):
+                self.assertTrue(pdb._pyrepl_available(tty_stdin, tty_stdout))
 
         with patch.dict(os.environ, {}, clear=True):
             mod = types.ModuleType("_pyrepl.main")
             mod.CAN_USE_PYREPL = True
-            with patch.dict("sys.modules", {"_pyrepl.main": mod}):
-                self.assertTrue(pdb._pyrepl_available())
+            with patch.dict("sys.modules", {"_pyrepl.main": mod}), \
+                 patch.object(os, "isatty", return_value=False):
+                self.assertFalse(pdb._pyrepl_available(tty_stdin, tty_stdout))
 
 
 class ChecklineTests(unittest.TestCase):
@@ -5002,9 +5015,14 @@ def test_stack_entry(self):
         p.set_trace(commands=['w', 'c'])
         self.assertIn("\x1b", output.getvalue())
 
-    @unittest.skipIf(not pdb._pyrepl_available(), "pyrepl is not available")
     def test_gen_colors(self):
+        # Do not use @unittest.skipIf(pdb._pyrepl_available()): that is
+        # evaluated at import time, before regrtest may redirect stdin.
+        if not pdb._pyrepl_available():
+            self.skipTest("pyrepl is not available")
         p = pdb.Pdb()
+        if p.pyrepl_input is None:
+            self.skipTest("pyrepl input is not available")
         gen_colors = p.pyrepl_input.gen_colors
 
         test_cases = [
@@ -5265,8 +5283,12 @@ def test_interact_completion(self):
         self.assertIn('84', output)
 
 
-@unittest.skipIf(not pdb._pyrepl_available(), "pyrepl is not available")
 class PdbTestReadlinePyREPL(PdbTestReadline):
+    @classmethod
+    def setUpClass(cls):
+        if not pdb._pyrepl_available():
+            raise unittest.SkipTest("pyrepl is not available")
+
     def _run_pty(self, script, input):
         # Override the env to make sure pyrepl is used in this test class
         return super()._run_pty(script, input, env={**os.environ})
diff --git a/Misc/NEWS.d/next/Library/2026-05-28-15-46-46.gh-issue-150544.SNsZ8z.rst b/Misc/NEWS.d/next/Library/2026-05-28-15-46-46.gh-issue-150544.SNsZ8z.rst
new file mode 100644
index 00000000000000..22f18affcb3ef7
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2026-05-28-15-46-46.gh-issue-150544.SNsZ8z.rst
@@ -0,0 +1,8 @@
+Fix ``pdb._pyrepl_available()`` to check whether the given stdin/stdout
+streams support pyrepl at call time, instead of relying only on the
+import-time ``_pyrepl.main.CAN_USE_PYREPL`` flag.  :class:`pdb.Pdb` now
+passes its streams to ``pdb._pyrepl_available()``.  This prevents
+:exc:`AttributeError` when ``pyrepl_input`` is ``None`` in non-TTY
+environments (such as :mod:`test` worker subprocesses) and avoids failures
+when ``stdin`` is replaced by doctest helpers without
+:meth:`~io.IOBase.fileno`.
diff --git a/Misc/NEWS.d/next/Tests/2026-05-28-15-49-57.gh-issue-150544.iN6-jy.rst b/Misc/NEWS.d/next/Tests/2026-05-28-15-49-57.gh-issue-150544.iN6-jy.rst
new file mode 100644
index 00000000000000..cadbeecd984a44
--- /dev/null
+++ b/Misc/NEWS.d/next/Tests/2026-05-28-15-49-57.gh-issue-150544.iN6-jy.rst
@@ -0,0 +1,3 @@
+Fix ``test.test_pdb`` to skip pyrepl-dependent tests at runtime instead of
+using import-time :func:`unittest.skipIf` on ``pdb._pyrepl_available()``.
+This fixes ``PdbTestColorize.test_gen_colors`` errors under ``make test``.