Objectives were to examine mechanisms underlying anabolic actions of cimaterol in skeletal muscle and to evaluate cimaterol's actions in hypothyroid and hyperthyroid rats. In the first study growing rats were fed either a control diet or a diet containing cimaterol for 10 days. In a second study sham-thyroidectomized and thyroidectomized (Tx) rats were assigned to one of 5 treatments: control (sham-Tx), Tx, Tx supplemented with cimaterol, Tx injected with triiodothyronine (T3), and Tx rats injected with T3 and supplemented with cimaterol. Effects of treatments on growth, muscle weights and urinary NT-methylhistidine (NMH) excretion were evaluated in both trials. Muscle was also collected for determinations of DNA, RNA, protein and activities of several proteolytic enzymes. Cimaterol caused muscle hypertrophy and increased urinary NMH excretion. Hence, anabolic actions of cimaterol may result from an increase in myofibrillar protein synthesis which exceeds changes in myofibrillar protein degradation. Urinary NMH excretion was reduced by thyroidectomy and increased in hyperthyroid rats and both hypothyroidism and hyperthyroidism were characterized by myopathy. Cimaterol increased muscle weights in hypothyroid but not in hyperthyroid rats. Therefore, cimaterol's anabolic properties are thyroid hormone-independent and antagonized by excess thyroid hormone. Anabolic actions of cimaterol in hypothyroid rat muscle were attributed to an action on protein synthesis because urinary NMH excretion was not affected by cimaterol but muscle RNA concentration was increased. Activities of cathepsins B, D and L and neutral proteinase were dose-related to thyroid status, however, were unrelated to cimaterol-dependent perturbations in NMH excretion. Control of muscle protein balance by thyroid hormones may involve regulation of these enzymes; however, control of muscle protein degradation by cimaterol is likely directed towards other proteolytic mechanisms or to mechanisms which alter susceptibility of myofibrillar proteins to degradation.