Eight schizophrenic inpatients without manifest comorbidity were longitudinally studied. The aim was to find whether clozapine, the prototype of atypical antipsychotic drugs, altered their serum concentrations of high sensitive C-reactive protein (hsCRP), an inflammatory marker of high clinical importance. Following first-time therapy with clozapine, predominantly as the sole antipsychotic for 8 weeks, hsCRP profiles increased subclinically by 600%. This rise, and the Spearman correlation between hsCRP values and corresponding leukocyte counts, was statistically significant. A one-time cross-section investigation of 25 long-term clozapine patients and 25 patient controls did not show an elevation of hsCRP under clozapine after 1 year and more. It is assumed that the clozapine-evoked increase of hsCRP is part of a transient acute-phase response. The underlying inflammatory process needs clarification.