Creatine kinase is an important enzyme in the energy metabolism of many cell types, including muscle cells. Increased serum levels of creatine kinase may serve as a marker of enhanced creatine kinase synthesis in muscle cells or muscle cell membrane damage. The purpose of this study was to compare serum creatine kinase levels in chronic psychosis patients treated with either atypical or conventional antipsychotics. Forty-nine patients, receiving clozapine (n=18), or olanzapine (n=18), or conventional agents (n=13), were studied. Fasting serum samples were analyzed for creatine kinase. A significant difference in median creatine kinase level was found among the treatment groups (p=0.03), in that the creatine kinase level was higher both in the patients receiving clozapine and in the patients receiving olanzapine, compared to that in patients receiving conventional antipsychotics, p=0.001 and p<0.0001, respectively. In addition, elevated creatine kinase levels above the upper limit of normal were found in 6 (17%) of the patients treated with clozapine or olanzapine, but in none of the patients treated with conventional agents. In summary, the present results indicate that therapy with atypical antipsychotics like clozapine and olanzapine, in contrast to conventional agents, may be associated with serum creatine kinase elevation.