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Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. PLA2 is enriched in neuronal membranes and plays an essential role in the functioning of membrane structures in the brain. Because a disordered phospholipid metabolism has been postulated in schizophrenia we started in 1985 a series of exploratory studies in an attempt to clarify the role of PLA2 in schizophrenic disorders. Our results can presently be summed up as follows: 1. Drug-free schizophrenics showed significantly higher PLA2 activity in serum and in plasma as compared with healthy controls as well as with nonschizophrenic psychiatric patients; the latter did not differ from the control group with regard to PLA2 activity. These findings suggest that increased PLA2 activity might be specific for schizophrenia. 2. The possibility that increased PLA2 activity is an artifact due to prior neuroleptic treatment could be ruled out as improbable by the findings that a) neuroleptic treatment significantly reduced PLA2 activity, and b) increased PLA2 activity was also found in first-onset, never-treated schizophrenic patients. 3. Increased PLA2 activity in schizophrenic patients was not caused by the entry of pancreatic enzyme into circulation. Our findings in serum rather suggest that the increment reflects increased intracellular enzyme activity. We speculate that our results might reflect an increment of the intraneuronal PLA2 activity in the brain. The activation of PLA2 in the brain was found to result in changes in neuronal function due to alterations in receptor sensitivity as well as in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathology of schizophrenia should be investigated in further experiments.