In 27 schizophrenic patients we investigated plasma levels of cytokines before the initiation of treatment and after the first, second and sixth week of treatment with the atypical antipsychotic agent clozapine. In addition, we did polysomnographic recordings in one schizophrenic patient prior to, during and following clozapine-induced fever. We found that independently of fever clozapine significantly increased the plasma levels of tumor-necrosis-factor a (TNFa) and soluble interleukin-2-receptor (sIL-2r) which were further increased by fever. Interleukin-6 (IL-6) was increased only together with fever and showed a significant positive correlation with clozapine-induced fever. The sleep recording of the fever night revealed severely disturbed sleep. Possible links between the clozapine-induced release of cytokines and clozapine's effect on night sleep are discussed.