The administration of the omega-3 fatty acid eicosapentaenoic acid (EPA) to a drug-naïve patient with schizophrenia, untreated with conventional antipsychotic medication, led to a dramatic and sustained clinical improvement in both positive and negative symptoms. This was accompanied by a correction in erythrocyte membranes of abnormalities in both n-3 and n-6 highly unsaturated fatty acids (HUFAs). Therefore EPA is able to reverse the phospholipid abnormalities previously described in schizophrenia. This reversal is associated with, and is likely to be the cause of, the clinical improvement. In particular, EPA appears to have reversed the depletion of not only n-3 HUFAs, but also of membrane arachidonic acid, possibly via inhibition of HUFA-specific phospholipase A(2), an enzyme which removes HUFAs from the S(N)2 position of membrane phospholipids, or by activation of a fatty acid coenzyme A ligase. Correction by EPA of abnormalities in both enzyme systems is not ruled out.