OBJECTIVE The Wada test is used to evaluate language lateralization and memory performance after inactivation of an isolated cerebral hemisphere. Methohexital a short-acting barbiturate has a history of use to induce interictal discharges during intraoperative corticography. We report a new finding of activation of lateralized periodic discharges (LPDs) after Methohexital injection. METHODS We retrospectively reviewed 174 consecutive adult patients who underwent Wada testing in preparation for epilepsy surgery (N = 129, 74%) or brain tumor resection (N = 45, 26%) at the University of Michigan to determine the frequency of induced periodic discharges by methohexital. RESULTS Four epilepsy patients (2.29%) had methohexital-induced LPDs within a median of 2 s (1-99 s) of the injection and lasting a median of 4 min (3-10 min) after a total of 7 injections. All LPDs occurred ipsilateral to the injection hemisphere in the known region of interictal epileptiform discharges. LPDs were not induced in brain tumor patients. In one patient, LPDs occurred during memory testing, and this patient's memory performance was below expectation based on pre-test neuropsychological testing. CONCLUSIONS Methohexital can induce LPDs in ipsilateral hemisphere and that can potentially affect memory performance. CONCLUSIONS This observation indicates that concurrent EEG monitoring during the Wada test is important and that induced discharges should be considered when interpreting Wada test results.