Sera from patients with muscle disease contain an inhibitor of creatine kinase (CK) which may lead to underestimation of CK activity. The inhibitor was dialyzable, but was not related to previously described low molecular weight inhibitors of CK. In a small group of patients with myositis, the amount of inhibitor present in serum was correlated with the severity of the illness. Our findings suggest that the CK inhibitor may be released into serum from injured muscle.