The purpose of this study was to investigate immune-inflammatory markers in schizophrenia and the effects of chronic treatment with clozapine, an atypical antipsychotic agent, on these variables. Toward this end, we measured interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R in the blood of 26 normal controls and 14 schizophrenic patients before and after treatment with clozapine. The sIL-2R and IL-6 levels were significantly higher in younger (< 35 years) schizophrenic subjects than in normal controls and older (> or = 35 years) schizophrenic subjects. The sIL-6R levels were significantly lower in schizophrenic subjects than in normal controls. Chronic treatment with clozapine significantly increased the blood concentration of sIL-2R; the increases in the latter were significantly related to the dose of clozapine but not to changes in severity of positive or negative symptoms. We conclude that: (a) schizophrenia in younger people is accompanied by increased IL-6 and sIL-2R secretion; and (b) subchronic treatment with clozapine increases sIL-2R levels. Increased plasma sIL-2R may be one mechanism by which neuroleptics exhibit their immunosuppressive effects.