Clinical definitions of schizophrenia are unreliable and difficult to use. The niacin flush test, which involves prostaglandin-induced vasodilatation, offers a method of exploring essential fatty acid metabolism in schizophrenic patients and may serve to define a subgroup of patients. In a multicentre study of schizophrenic patients with negative symptoms, we have examined the clinical accompaniments of the niacin response. Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids. Conversion from non-flushing to flushing during the 6 month supplementation period was predicted by an increase in arachidonic acid levels in red blood cell membranes irrespective of nature of supplementation. In this study, patients were selected for their negative symptoms and, therefore, it was not surprising that further measures of negative or positive symptoms did not predict flushing. However, an increased score for affective symptoms was significantly associated with a positive flush response. The stability of the niacin test needs to be examined in relation to the periodicity of symptoms in schizophrenia and manic depressive illness. New information on the anandamide system suggests that it may be associated with periodic phenomena and should be investigated in relation to the niacin test.