Few guidelines exist for the use of corticosteroid therapy in polymyositis-dermatomyositis (PM-DM). We retrospectively examined the relationship between serum creatine kinase (CK), muscle strength and the dosage and method of administration of prednisone in 30 patients with PM-DM observed monthly for a minimum of one year. Forty-two corticosteroid treated episodes of proximal muscle weakness associated with CK elevations formed the final study group. Each patient course was designated as having a good or poor biochemical and clinical outcome based on predetermined criteria. Adherence to 3 principles predicted a favorable biochemical and clinical outcome in the treatment of myositis: (1) administration of an adequate initial (loading) corticosteroid dose; (2) continuation of the initial dose until or after the time that the serum CK had become normal; and (3) a slow corticosteroid taper rate. Achievement of a CK within the low normal range predicted a prolonged biochemical remission, and a rise of CK within the normal range signalled a subsequent biochemical and clinical relapse. Tapering the corticosteroid dose when the CK was elevated frequently resulted in a further increase in CK. These observations allowed us to develop practical guidelines for the management of PM-DM.