We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research.