Phencyclidine and related compounds such as MK-801 produce psychotic symptoms, which closely resemble schizophrenia. MK-801 causes lesions in different corticolimbic regions including the medial entorhinal cortex (mEC). Using electrophysiological recordings in brain slices we tested whether several hours of systemic administration of MK-801 affect stimulus-induced field potentials (FPs) in the mEC. Stimulus-induced FPs were selectively reduced in layer III, but not in layers II and V of the mEC. In contrast, MK-801 applied acutely over the bath in low concentration had no significant effect on evoked FPs. Since the principal cells of layer III project directly to area CA1 and the subiculum, the selective effects of MK-801 may have implications for the transfer of information to the hippocampus.