In order to examine the pH dependency of Cd effects on cardiac muscle, the electrical and mechanical activities in the bullfrog heart were investigated in relation to various external pHs and concentrations of Cd. The amplitude and duration of the action potential or the spontaneously beating frequency in the atrium were not significantly affected during the 3-min administration of various concentrations of Cd in a range from pH 6 to 10, but the isotonic contraction at the end of the same period was greatly altered: the lower the external pH the more Cd decreased the contractility of the atrium. This pH dependency of Cd effects was also observed in SO₄-Ringer's solution whose anions, SO₄, were more impermeable than Cl. Decrease in contractility in Cd- Ringer's solution was counteracted by excess Ca. The lower the pH of the Cd-Ringer's solution, the more Ca was necessary to counteract an equal amount of Cd. The amount of Cd-uptake into the atrium was analyzed after soaking the atrium in various concentrations of Cd-Ringer's solution. The higher the concentration of external Cd, the larger the Cd-uptake into the atrium. No pH dependency, however, was observed in this relationship. This suggests that probably only a small fraction of total Cd-uptake interacts with Ca-binding sites which is specific to contraction, and causes the Cd-induced decrease in contractility. This process is considered to be pH-dependent. However, most Cd-uptake into cardiac muscle is pH-independent and may be nonspecific to contraction.