The response of isolated left atria of guinea pigs to carbachol was measured in the presence and during washout of the drug. The time courses of the negative inotropic effect and of the rate of shortening in action potential duration were compared. The initial rapid decline in force of contraction was followed by a slowly developing partial recovery (fading). After removal of the drug, a transient phase of hypercontractility was observed before the control level was reached again. In contrast to the mechanical effect, the drug-induced shortening of the action potential duration proceeded monophasically. The fading and hypercontractility phenomena shown by the mechanical response to the drug were influenced by the stimulation rate and by the presence of ouabain. From the dissociation of electrical and mechanical effects it is concluded that fading and hypercontractility are not due to changes of receptor sensitivity but reflect a change in cellular calcium distribution.