Autoimmune mechanisms have been postulated to play a role in the pathogenesis of schizophrenia. Recently, increased numbers of B lymphocytes expressing the CD5 (Leu-1) surface antigen have been observed in patients with certain autoimmune diseases. In the present study, approximately 30% of schizophrenic patients (11/34) were found by cytofluorometric methods to have similarly increased levels of circulating CD5+ B cells compared with 6% (2/33) of healthy individuals and 5% (1/20) of patients with bipolar affective disorder. In schizophrenic patients with a "high" CD5+ B-cell phenotype, the percentage of B cells expressing the CD5 surface marker (mean +/- SEM, 52.4% +/- 3.5%) was comparable to that reported for patients with rheumatoid arthritis and significantly greater than that reported for patients with bipolar affective disorder (25.7% +/- 2.5%) and healthy controls (31.0% +/- 1.8%). Schizophrenic patients with high levels of CD5+ B cells had increased numbers of total B cells compared with control subjects and patients with low levels of CD5+ B cells. An elevation in CD5+ B cells may delineate a subgroup of schizophrenic patients whose disease has an underlying autoimmune and/or genetic cause.