Effects of dantrolene sodium on electrical and mechanical activity of guinea-pig ventricular muscles were examined. The application of 2×10^-5M of dantrolene caused a decrease of developed tension by 31% of the control level without noticeable changes in resting membrane potential, amplitude and maximum upstroke velocity (V_max) of action potentials, and action potential duration. Negative inotropic effects of dantrolene appeared after 10min application and reached almost a plateau after 15-20min. Neither amplitude of the slow inward current nor the outward current on depolarization were affected by dantrolene. When muscle preparations were superfused with the low-K⁺, high-Ca²⁺ solution, they developed delayed afterdepolarizations and aftercontractions. The application of 2×10^-5 M of dantrolene did not reduce amplitudes of both delayed afterdepolarizations and aftercontractions, but depressed twitch tension to 74% of the control level. Dantrolene did not change the amplitude of the transient inward current observed under the low-K⁺, high-Ca²⁺ condition. These results suggest that a primary site of action of dantrolene is not the sarcolemma of ventricular myocardium, but possibly the Ca²⁺ releasing process from the sarcoplasmic reticulum. Its action is further indicated to affect the process of depolarization-induced Ca²⁺-release, either directly or indirectly rather than to inhibit Ca²⁺ -induced Ca²⁺ -release.