Synaptic alterations have been suggested, largely on theoretical grounds, to occur in the brain in schizophrenia. The messenger RNA encoding synaptophysin, a presynaptic terminal protein, is reduced in the medial temporal lobe in the disease, but immunocytochemical and immunoblotting data have not produced clear evidence for a loss of the encoded protein. Here we have used immunoautoradiography with an antisynaptophysin monoclonal antibody and a 35S-labelled secondary antibody in medial temporal lobe sections from 11 schizophrenics and 14 matched controls. In the schizophrenic cases there was an overall loss of synaptophysin (P < 0.02). Analysis by subfield showed significant reductions in the right dentate gyrus molecular layer, subiculum and parahippocampal gyrus, with similar trends in most other subfields. These data confirm that synaptophysin expression is decreased within the medial temporal lobe in schizophrenia. In the respect that synaptophysin is a marker of synaptic density, our findings suggest that reduced synaptic density may be a feature of the molecular neuropathology of the disease.