Several lines of evidence implicate altered phospholipid-dependent signal transduction (PDST) in the pathophysiology of schizophrenia. Niacin induces vasodilation through mechanisms requiring intact PDST. Thus, an altered response to a challenge dose of niacin may reflect disturbances in these signalling processes in this disorder. In the present study, niacin-induced vasodilation was estimated quantitatively in schizophrenic and comparison bipolar affective disorder and healthy subjects using thermocouple sensors to measure the change in skin temperature relative to core body and ambient room temperature. Twelve (42.9%) of 28 schizophrenic subjects did not vasodilate in response to a 200-mg niacin challenge dose, whereas only 1 of 18 (6%) bipolar disorder subjects and none of 28 controls showed impaired response (Fisher's Exact Test, p < .0001). These findings support the notion that the schizophrenic syndromes are biochemically heterogeneous and suggest the existence of a subgroup of schizophrenic subjects in whom phospholipid-dependent signalling responses may be impaired.