The effects of iontophoretically applied N-methyl-D-aspartate (NMDA) were assessed in human neocortical and caudate neurons. NMDA depolarized cell membranes, decreased input conductances and induced firing. The discharge patterns differed in the two areas studied. In neocortex, NMDA produced repetitive spikes or bursts. In caudate, it induced slow, rhythmic plateau depolarizations accompanied by an initial burst of action potentials, followed by low amplitude, long duration spikes. After hyperpolarizations were seen after each depolarization in the caudate. These variations in patterns of excitation may relate to differences in local circuits intrinsic to each region, and/or to membrane conductances specific to each type of cell.