Although abnormalities of the immune system have been described in depression, information on serological alteration in acutely manic patients has been scarce. The present study undertook to investigate the levels of C-reactive proteins, circulating immune complexes, total immunoglobulins and immunoglobulin subclasses, complement proteins C3, C4, C6 and Factor B in the sera of 45 patients suffering from an acute manic episode. The findings were compared with assessments on the sera of 45 controls. The results demonstrate a number of significant differences between patients and controls. Whilst levels of immunoglobulin D were significantly lower, the levels of total immunoglobulin and immunoglobulin G1, complement proteins C3, C6 and Factor B were raised in the patient group when compared with the controls. Our results suggest a relationship between acute mania and immunological parameters associated with acute phase responses. Copyright © 2002 John Wiley & Sons, Ltd.