There is some evidence that schizophrenia may be accompanied by alterations in cell-mediated immunity (CMI) and that antipsychotic agents may modulate CMI. The purpose of this study was to investigate the plasma levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin-receptor (TfR) in schizophrenia and mania, and the effects of treatment with neuroleptics or mood stabilizers on these variables. The subjects were 14 schizophrenic patients, 10 manic patients and 21 healthy volunteers. The above immune variables were measured in baseline conditions and after treatment with neuroleptics in schizophrenic patients and valproate in manic patients. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in the combined group of psychotic patients than in healthy volunteers. Plasma IL-6 was significantly higher in schizophrenic patients, while plasma sIL-6R and sIL-2R were significantly higher in mania than in normal controls. In schizophrenic patients, plasma levels of IL-6, sIL-6R and TfR were significantly lower after treatment with neuroleptics than before treatment. No significant effects of valproate on the immune-inflammatory markers could be found in the manic patients. It is suggested that activation of CMI may occur in both schizophrenia and mania and that neuroleptics may have immunosuppressive effects through suppression of IL-6 or IL-6R-related mechanisms.