A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-gamma (IFN-gamma) may be lowered. In a longitudinal design, we studied the production of both IFN-gamma and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-gamma and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-gamma and IL-2 was significantly lower in patients than in controls throughout the whole investigation period (T1-T3). The productions of both cytokines were significantly correlated in controls (r = 0.60, P </= 0.001) as well as in patients with schizophrenia (mean production T1-T3: r = 0.71, P </= 0.001). No associations between cytokine measurements and psychopathology or age-at-onset could be found. Our findings of lowered and correlated IFN-gamma and IL-2 production indicate that alterations in the cytokine system of patients with schizophrenia might resemble those in autoimmune disorders. It is suggested that these immunological abnormalities are associated with acute exacerbation, rather than with a clinical subtype of schizophrenia.