The toxic effects of HgCl2 (1, 2.5, 5, and 10 microM) were studied in isolated, isometrically contracting rat papillary muscles and frog ventricular strips. In rat papillary muscles 1 microM Hg2+ produced a small increase in the force of contraction. Higher concentrations of HgCl2 produced a dose-dependent decrease in contractile force. The rate of force development was affected differently, increasing at 1 and 2.5 microM Hg2+ and decreasing to control levels at 5 and 10 microM Hg2+. This was the result of a progressive reduction in the time to peak tension observed when HgCl2 concentrations increased. This effect probably reflects the binding of Hg2+ to SH groups inducing Ca2+ release from the sarcoplasmic reticulum. The relative potentiation of postrest contractions was used as an index of sarcoplasmic reticulum activity. It was measured after pauses of increasing duration and was reduced at concentrations of 1 microM Hg2+ when compared to that of the control. A further decrement in the relative potentiation was observed with higher Hg2+ concentrations, indicating that the activity of the sarcoplasmic reticulum was depressed by mercury in a dose-dependent manner. Tetanic contractions were also studied in the rat myocardium. The tetanic tension did not change during treatment with 1 microM Hg2+ but decreased with 5 microM Hg2+, suggesting a toxic effect on the contractile proteins only at high Hg2+ concentrations. Frog ventricular strips were studied using the same HgCl2 concentrations and no effects on either force or relative potentiation were observed. These findings suggest that Hg2+ promotes dose-dependent toxic effects on heart muscle via actions on the sarcolemma, the sarcoplasmic reticulum, and contractile proteins.