Dantrolene causes skeletal muscle relaxation in animals without prominent CNS actions, and it has little or no measurable effect on smooth or cardiac muscle. Dantrolene reduces rigidity in decerebrate cats. Unlike centrally acting muscle relaxants, it has no preferential effect on polysynaptic flexor reflexes and still produces its maximum effect on the muscle twitch in an isolated, neurally intact, perfused hindlimb. Dantrolene blocks the twitch response when stimulated through the motor nerve in a way different from the action of tubocurarine or decamethonium. It inhibits direct twitch responses in denervated muscle and is equally effective in attenuating the direct and indirect twitch responses. It is hypothesized that dantrolene causes skeletal muscle relaxation by a direct action on muscle at a site beyond the neuromuscular junction.