There have been few studies focusing on the creatine phosphokinase (CPK) elevations in chronic psychiatric patients. The survey was conducted prospectively to investigate the incidence and risk factors of CPK elevations in chronic psychiatric patients during a 2-year follow-up period. Sixteen of 32 (50%) patients had maximums of more than 230 U/l (upper limit of our normal range) and 7 (22%) patients had maximums of more than 500 U/l. Surprisingly, 4 (13%) patients had maximums of more than 1,000 U/l after exercises such as swimming and walking. Nonetheless, none of the 16 patients with the CPK elevations developed severe conditions such as rhabdomyolysis despite an absence of therapeutic intervention, and their CPK elevations were proven to be benign. According to the path analysis, usual physical activity and neuroleptic doses seemed to underlie CPK elevations directly. The present findings suggest that not a few chronic psychiatric inpatients may have at least one CPK elevation per 2 years. Patients engaging in more physical activity or receiving higher neuroleptic doses are at greater risk of developing such CPK elevations. However, most of these increases are benign, and it is not considered necessary to treat them.