The 'membrane hypothesis' of schizophrenia postulates a disturbance in the metabolism and structure of membrane phospholipids resulting in a disturbance in the function of neuronal membrane proteins. Most studies exploring this hypothesis have examined components of peripheral blood. Since it may be questioned if these peripheral measurements reflect changes in the brain, we studied the fatty acid composition of glycerophospholipids in brain tissue. As a marker for synaptic density, we also measured the synaptic vesicle protein synaptophysin. Brain tissue (gyrus cinguli) from 11 schizophrenic patients (mean age 80 +/- 10 years) and 13 controls (mean age 75 +/- 14 years) was examined. The glycerophospholipid fatty acids were determined by gas chromatography. Synaptophysin protein level was determined using quantitative immunoblotting followed by Western blotting. There were no significant differences between the groups in the total or in any individual level of fatty acids, either in the n - 6 or n - 3 series. The level of synaptophysin was significantly p = (0.002) decreased in the schizophrenic group(0.73 + 0.18) as compared with the control group (1.02 + 0.21). The normal pattern and concentration of glycerophospholipids fatty acids found in the present study do not support the membrane hypothesis of schizophrenia. The possibility of a type II error should, however. be considered. On the other hand, the reduced synaptophysin' levels in the gyrus cinguli demonstrate that biological differences can be revealed in this relatively small sample. This also lends further support to the notion that a synaptic disturbance or loss is of importance in the pathogenesis of schizophrenia.