The intracellular enzyme phospholipase A2 (PLA2) plays an essential role in the breakdown of membrane phospholipids, which regulate the physicochemical properties of the cell membrane. In the brain PLA2 has been reported to influence receptor function and signal transduction. Regarding dopaminergic neurons, data from animals experiments and from binding studies suggest that PLA2 activation reduces dopaminergic neurotransmission. In the present study we investigated intracellular PLA2 in platelets from 31 DSM-III-R paranoid schizophrenic patients (15 neuroleptic-naive) compared to 31 healthy individuals and to 31 non-schizophrenic psychiatric controls, both matched to the schizophrenics by age and sex. Platelet PLA2 activity was significantly increased in schizophrenics as compared to healthy and to psychiatric controls. Neuroleptic treatment reduced significantly the enzyme activity. Our findings in platelets suggest an accelerated breakdown of membrane phospholipids in schizophrenia. An accelerated phospholipid breakdown has also been reported in the frontal cortex from schizophrenic patients. Further studies should clarify whether increased PLA2 in the brain, as observed in platelets, could contribute to a frontal dysfunction in schizophrenia.