Wada testing remains an important component of pre-surgical testing to assess the feasibility of temporal lobectomy for patients with intractable epilepsy. In this procedure, an anesthetic is injected into either internal carotid artery while memory and language testing is performed, simulating the effect of temporal lobe resection. The mechanism remains poorly understood because the hippocampal vasculature is predominantly via the posterior circulation. We recorded hippocampal EEG during bilateral methohexital Wada testing in three patients who had previously been implanted with a responsive neurostimulation system (RNS) to determine the effect of the injections on hippocampal activity. In all six injections from three patients, methohexital caused immediate, transient increases in hippocampal spikes. With at least two of these injections, the electrographic changes were consistent with electrographic seizures. In all cases, the epileptiform activity was not apparent on scalp EEG and was without obvious clinical correlate other than the negative findings expected from the anesthetic. The results demonstrate the utility of intracranial EEG during Wada testing and suggest that the elicitation of seizures or continuous spiking might contribute to dysfunction of the hippocampus during the Wada test. We hypothesize that this effect is due to disconnection and disinhibition of medial temporal structures.