Neuropathological studies have demonstrated deficits of GABAergic interneurons in the hippocampus in schizophrenia. and selective deficits in some GABAergic sub-populations defined by calcium-binding proteins (CBPs) have been reported in the cortex in schizophrenia. In the present study, the relative densities of cells immunoreactive for the CBPs parvalbumnin (PV) and calretinin (CR) were determined in hippocampal tissue sections taken from patients with schizophrenia, bipolar disorder and major depression and from matched control subjects (15 per group). No significant difference in the density of CR-immunoreactive neurons was found between subject groups. Relative to normal controls, schizophrenic patients showed a significant and profound deficit in the relative density of PV-immunoreactive neurons in all hippocampal sub-fields. These reductions were more apparent in male than female schizophrenic patients, and were unrelated to antipsychotic drug treatment, age or duration of illness. The density of PV-immunoreactive neurons did not differ significantly from controls in the depression group, although a trend toward decreased relative density of PV-immunoreactive neurons was apparent in bipolar disorder that reached significance in one sub-field. The findings provide further evidence to support a profound and selective abnormality of a sub-population of GABAergic neurons in the hippocampus in schizophrenia.