The effects of crotoxin, isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus, were investigated on isolated guinea pig hearts, perfused with Locke solution, by the Langendorff method. The cardiac beats and the electrocardiogram were simultaneously registered and the creatine kinase (CK) activity of the perfusate measured. Crotoxin was infused (4.5 x 10(-8) M and 2.3 x 10(-7) M) into the heart during 90 min, and induced a remarkable decrease in the contractile force, without a significant reduction of heart rate, increased the P-R interval and displaced the S-T segment. The activity of CK only increased in the late phases of the experiments, when the force of contraction was below 25% of the control value. Arrhythmias were uncommon and no alterations of QRS duration or Q-Tc interval were observed. The reduction of the contractile force and the increase in CK activity were completely prevented by bovine serum albumin, whereas lanatoside C did not interfere with the toxin action. A bolus injection of crotoxin (11 +/- 2 nmoles) also induced a decrease of contractile force without reduction of heart rate. This decrease of force was partially prevented by indomethacin, but not by atropine. It is suggested that the reduction of contractile force evoked by crotoxin is due probably to release of free fatty acids and lysophospholipids (initial effect) and to a cellular lesion (late effect).