Previous studies have shown decreased erythrocyte membrane (EM) Na,K-ATPase activity in chronic patients suffering from schizophrenia (SCH). There are no data about changes at the onset of psychosis and enzyme kinetics. Increased lipid peroxidation could be responsible for alterations in Na,K-ATPase activity. Substrate kinetics pattern of EM Na,K-ATPase and levels of lipid peroxides in plasma and erythrocytes were measured in (1) patients with first episode of psychosis (n=20) before medication and after the first 3 weeks of treatment, (2) chronic medicated schizophrenic patients (n=52) in the exacerbation phase, and (3) age- and sex-matched control subjects (n=30). All patients were assigned to groups with predominantly positive or predominantly negative symptoms on the basis of their scores on Positive and Negative Syndrome Scale (PANSS). In first-episode patients with predominantly negative symptoms before treatment, uncompetitive inhibition of Na,K-ATPase was noticed. The first-episode patients with predominantly positive symptoms had increased enzyme catalytic activity. After 3 weeks of treatment, activities were normalized in both groups. Among chronic patients, uncompetitive inhibition was found only in patients with predominantly negative symptoms. Plasma lipid peroxides (thiobarbituric acid-reactive substances [TBARS]) were elevated in both groups of patients with first episode of psychosis. Despite the presence of peroxidative injury indicative for the loss of membrane phospholipid essential fatty acids, the activities of Na,K-ATPase differ between SCH (+) and SCH (-) patients.