diff --git a/doc/changelog.rst b/doc/changelog.rst
index 369142bf..dfc43287 100644
--- a/doc/changelog.rst
+++ b/doc/changelog.rst
@@ -6,6 +6,7 @@ ChangeLog
 
 Bugfixes:
 
+- Disallow creating an instruction targeting a pseudo/instrumented opcode PR #133
 - Fixes encoding of 0 as a varint PR #132
 - Correct spelling of "INTRINSIC" in several places; this affected
   some ops in Python 3.12.  PR #131
diff --git a/src/bytecode/instr.py b/src/bytecode/instr.py
index 95e1c43d..e927cdf4 100644
--- a/src/bytecode/instr.py
+++ b/src/bytecode/instr.py
@@ -14,7 +14,9 @@
 
 import bytecode as _bytecode
 
-# --- Instruction argument tools and abstractions
+# --- Instruction argument tools and
+
+MIN_INSTRUMENTED_OPCODE = getattr(_opcode, "MIN_INSTRUMENTED_OPCODE", 256)
 
 # Instructions relying on a bit to modify its behavior.
 # The lowest bit is used to encode custom behavior.
@@ -734,6 +736,12 @@ def _set(self, name: str, arg: A) -> None:
         except KeyError:
             raise ValueError(f"invalid operation name: {name}")
 
+        if opcode >= MIN_INSTRUMENTED_OPCODE:
+            raise ValueError(
+                f"operation {name} is an instrumented or pseudo opcode. "
+                "Only base opcodes are supported"
+            )
+
         self._check_arg(name, opcode, arg)
 
         self._name = name
diff --git a/tests/test_instr.py b/tests/test_instr.py
index 4952ab2a..1437b87a 100644
--- a/tests/test_instr.py
+++ b/tests/test_instr.py
@@ -138,6 +138,12 @@ def test_repr(self):
         self.assertIn("arg", r)
         self.assertIn("_x_", r)
 
+    def test_reject_pseudo_opcode(self):
+        if sys.version_info >= (3, 12):
+            with self.assertRaises(ValueError) as e:
+                Instr("LOAD_METHOD", "x")
+            self.assertIn("is an instrumented or pseudo opcode", str(e.exception))
+
     def test_invalid_arg(self):
         label = Label()
         block = BasicBlock()