Mercury reduces twitch and tetanic force development in isolated rat papillary muscles, and a putative toxic effect on the contractile machinery has been suggested. Based on that, the actions of HgCl2 on the myosin ATPase activity of the left ventricular myocardium were investigated. Samples for assay of myosin ATPase activity were obtained from rats' left ventricles. Increasing concentrations of HgCl2 reduced dose-dependently the activity of the myosin ATPase. This reduction was observed even at very small concentrations, 50 nM HgCl2. This effect was dependent on the presence of SH groups in the myosin molecule since DTT and glutathione protected the myosin ATPase against toxic effects of mercury; full activity being restored by using 500 nM DTT or 500 nM glutathione. Results also suggested that the metal acts as an uncompetitive inhibitor with a Ki of 200 nM HgCl2. Our results suggest that mercury reduces the activity of the myosin ATPase by an uncompetitive mechanism at a very low dose that does not depress force. DTT and glutathione are effective for protection against the actions of mercury suggesting that SH groups might be the sites of action of the metal on the myosin molecule.