Dose-response curves for the negative inotropic effect and the shortening of the action potential duration induced by carbachol were established in isolated left atria of rats and guinea pigs. Various experimental conditions were chosen, including two different frequencies of stimulation (0.1 and 2 Hz) and the application of ouabain. Under all experimental conditions, very similar dose-response curves were obtained for the electrical activity. In contrast, the dose-response curves for the negative inotropic effect were markedly affected, since carbachol was less effective in depressing contractile force at 0.1 Hz and in the presence of ouabain. A lesser negative inotropic effect of carbachol could also be demonstrated after a single prolongation of the beat interval for various periods of time. It is suggested that the differences in the dose-response curves for the electrical and mechanical activities reflect changes in the efficacy of excitation-contraction coupling.