We investigated the effects of troglitazone, a new orally active hypoglycemic agent, on the voltage-dependent L-type Ca2+ current in single cardiac ventricular myocytes of guinea pigs by the whole-cell voltage clamp technique. Troglitazone blocked the Ca2+ currents in a concentration-dependent manner. The inhibitory effect was more potent at the holding potential (HP) of - 50 mV than at - 80 mV. The half-maximum inhibiting concentration (IC50) of troglitazone was 0.8 microM with the Hill coefficient of 0.84 at -50 mV HP. In contrast, the IC50 value was higher than 10 microM at -80 mV HP. These results suggest that troglitazone at therapeutic concentrations inhibit the Ca2+ channels and may exert cardioprotective effects in diabetic conditions.