diff --git a/petab/v2/C.py b/petab/v2/C.py
index 5bb73980..e680450e 100644
--- a/petab/v2/C.py
+++ b/petab/v2/C.py
@@ -285,6 +285,9 @@
 #: separator for multiple parameter values (bounds, observableParameters, ...)
 PARAMETER_SEPARATOR = ";"
 
+#: The time symbol for use in any PEtab-specific mathematical expressions
+TIME_SYMBOL = "time"
+
 
 __all__ = [
     x
diff --git a/petab/v2/lint.py b/petab/v2/lint.py
index 0780b340..2f11cc61 100644
--- a/petab/v2/lint.py
+++ b/petab/v2/lint.py
@@ -42,6 +42,7 @@
     "CheckObservablesDoNotShadowModelEntities",
     "CheckUnusedConditions",
     "CheckPriorDistribution",
+    "CheckInitialChangeSymbols",
     "lint_problem",
     "default_validation_tasks",
 ]
@@ -713,6 +714,62 @@ def run(self, problem: Problem) -> ValidationIssue | None:
         return None
 
 
+class CheckInitialChangeSymbols(ValidationTask):
+    """
+    Check that changes of any first period of any experiment only refers to
+    allowed symbols.
+
+    The only allowed symbols are those that are present in the parameter table.
+    """
+
+    def run(self, problem: Problem) -> ValidationIssue | None:
+        if not problem.experiments:
+            return None
+
+        if not problem.conditions:
+            return None
+
+        allowed_symbols = {p.id for p in problem.parameters}
+        allowed_symbols.add(TIME_SYMBOL)
+        # IDs of conditions that have already been checked
+        valid_conditions = set()
+        id_to_condition = {c.id: c for c in problem.conditions}
+
+        messages = []
+        for experiment in problem.experiments:
+            if not experiment.periods:
+                continue
+
+            first_period = experiment.sorted_periods[0]
+            for condition_id in first_period.condition_ids:
+                if condition_id in valid_conditions:
+                    continue
+
+                # we assume that all referenced condition IDs are valid
+                condition = id_to_condition[condition_id]
+
+                used_symbols = {
+                    str(sym)
+                    for change in condition.changes
+                    for sym in change.target_value.free_symbols
+                }
+                invalid_symbols = used_symbols - allowed_symbols
+                if invalid_symbols:
+                    messages.append(
+                        f"Condition {condition.id} is applied at the start of "
+                        f"experiment {experiment.id}, and thus, its "
+                        f"target value expressions must only contain "
+                        f"symbols from the parameter table, or `time`. "
+                        "However, it contains additional symbols: "
+                        f"{invalid_symbols}. "
+                    )
+
+        if messages:
+            return ValidationError("\n".join(messages))
+
+        return None
+
+
 class CheckPriorDistribution(ValidationTask):
     """A task to validate the prior distribution of a PEtab problem."""
 
@@ -1058,10 +1115,7 @@ def get_placeholders(
     CheckValidParameterInConditionOrParameterTable(),
     CheckUnusedExperiments(),
     CheckUnusedConditions(),
-    # TODO: atomize checks, update to long condition table, re-enable
-    # TODO validate mapping table
-    CheckValidParameterInConditionOrParameterTable(),
-    CheckAllParametersPresentInParameterTable(),
-    CheckValidConditionTargets(),
     CheckPriorDistribution(),
+    CheckInitialChangeSymbols(),
+    # TODO validate mapping table
 ]
diff --git a/tests/v2/test_lint.py b/tests/v2/test_lint.py
index 12973d86..82917902 100644
--- a/tests/v2/test_lint.py
+++ b/tests/v2/test_lint.py
@@ -39,6 +39,31 @@ def test_check_incompatible_targets():
     assert "overlapping targets {'p1'}" in error.message
 
 
+def test_validate_initial_change_symbols():
+    """Test validation of symbols in target value expressions for changes
+    applied at the start of an experiment."""
+    problem = Problem()
+    problem.model = SbmlModel.from_antimony("p1 = 1; p2 = 2")
+    problem.add_experiment("e1", 0, "c1", 1, "c2")
+    problem.add_condition("c1", p1="p2 + time")
+    problem.add_condition("c2", p1="p2", p2="p1")
+    problem.add_parameter("p1", nominal_value=1, estimate=False)
+    problem.add_parameter("p2", nominal_value=2, estimate=False)
+
+    check = CheckInitialChangeSymbols()
+    assert check.run(problem) is None
+
+    # removing `p1` from the parameter table is okay, as `c2` is never
+    #  used at the start of an experiment
+    problem.parameter_tables[0].parameters.remove(problem["p1"])
+    assert check.run(problem) is None
+
+    # removing `p2` is not okay, as it is used at the start of an experiment
+    problem.parameter_tables[0].parameters.remove(problem["p2"])
+    assert (error := check.run(problem)) is not None
+    assert "contains additional symbols: {'p2'}" in error.message
+
+
 def test_invalid_model_id_in_measurements():
     """Test that measurements with an invalid model ID are caught."""
     problem = Problem()