The effects of dihydropyridine derivatives on contractile activity were examined in single fibers of frog skeletal muscles. Both nifedipine and Bay K 8644 enhanced twitch responses regardless of the presence or absence of Ca2+ without any effects on the resting membrane potential, evoked action potential and Ca2+ sensitivity of the contractile machinery. Twitch responses enhanced by Bay K 8644, but not by nifedipine, were partially reduced by adenine, an inhibitor of Ca(2+)-induced Ca2+ release from sarcoplasmic reticulum, suggesting the involvement of Ca(2+)-induced Ca2+ release in Bay K 8644-induced potentiation of the twitches. Both nifedipine and Bay K 8644 caused a dose-dependent potentiation of K+ contractures without any effects on the membrane potential in the presence of Ca2+, but inhibited the contractures in the absence of Ca2+. These results suggest that dihydropyridine derivatives modify contractile activities of skeletal muscles by modulating the dihydropyridine receptors on the surface of T-tubules acting as voltage sensors.