Recent studies have reported an increase in GABA A receptor binding activity in several key corticolimbic regions, including the hippocampal formation, of postmortem schizophrenic brain. Because this change has been postulated to represent a compensatory upregulation of this receptor, the current report has sought to determine whether a decrease of glutamate decarboxylase (GAD), the enzyme responsible for the synthesis of GABA, may also be present in the hippocampus of schizophrenic subjects. A standard immunoperoxidase technique, together with a computer-assisted microscopic analysis, has been employed to evaluate the distribution of the 65 kDalton isoform of GAD (GAD 65 ) in 12 normal controls and 13 schizophrenic subjects matched for age and postmortem interval (PMI). The results show no significant difference in the density of GAD 65 -immunoreactive (-IR) puncta in contact with pyramidal neurons (PN), nonpyramidal neurons (NP), or neuropil (NPL) in sectors CA 1-4 and their various sub-laminae. When the data were considered in relation to neuroleptic exposure, a significant positive correlation between the density of GAD 65 -IR puncta and drug dose was found on both PNs (r ϭ 0.814, P ϭ 0.002; r ϭ 0.777, P ϭ 0.005, respectively) and NPs (r ϭ 0.673, P ϭ 0.023; r ϭ 0.672, P ϭ 0.024, respectively) in sectors CA 4 and CA 3 . A similar result was found in the stratum oriens of CA 3 (r ϭ 0.704, P ϭ 0.016) and CA 2 (r ϭ 0.774, P ϭ 0.009). In each instance, two neuroleptic free schizophrenics showed the lowest density of GAD 65 -IR puncta. There was no significant relationship between the density of GAD 65 -IR puncta with either age or PMI. Taken together with previous data showing an upregulation of GABA A receptor activity in sectors CA 3 and CA 2 , particularly the stratum oriens, this study provides further evidence in support of the hypothesis that an intrinsic defect of GABAergic activity may occur in the hippocampal formation of schizophrenic patients and show dose-related increases in relation to neuroleptic exposure.