The effects of thyrotoxicosis on the contractile properties and development of muscle fatigue in the slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles were examined in rats given 3 mg of L-thyroxine and 1 mg of L-triiodothyronine per kilogram of diet for 6 weeks. The hormone treatment produced significant decreases in the contraction time, one-half relaxation time, and twitch tension in the SOL, while the peak rate of tension development (+ dP/dt) and decline (- dP/dt) in this muscle were elevated. Additionally, the force-frequency curve was shifted to the right and, thus, resembled the curve of a normal fast-twitch muscle. In contrast, the contractile properties of the fast EDL were relatively unaltered by the hormone administration. Thyrotoxicosis also changed the SOL response to contractile activity as twitch tension, + dP/dt, and - dP/dt remained high, and a faster decline in muscle glycogen and an increase in lactate occurred compared to control muscles. These results clearly demonstrate a preferential effect of thyroid hormone on slow compared to fast skeletal muscle.