Phosphatidylserine (PS) has recently been reported to be a specific inhibitor of B-type monoamine oxidase (MAO-B). The effect of added PS liposomes on platelet MAO-B activity was examined in two schizophrenic groups (paranoid and a mixture of residual/undifferentiated) and in normal controls. PS was a potent partial-mixed-uncompetitive inhibitor of the platelet enzyme, whereas other phospholipids tested were without effect. The PS concentration required for 50% inhibition was significantly higher for the paranoid relative to the residual/undifferentiated group and controls. This correlated with a lower mean basal MAO-B activity in this group. Hill plots, as a measure of the concentration dependence of PS sensitivity, however, revealed a similarity between the two schizophrenic groups in regard to inhibitor binding properties. Mean Hill coefficients for both groups were significantly different from the controls. The results were consistent with an in vivo role for PS as an allosteric regulator of platelet MAO-B.