The chronotropic effects of digoxin and deslanoside were studied in canine atria cross-perfused with heparinized arterial blood from donor dogs. Intravenous injections of either drug (100 micrograms/Kg) into the donor dog produced bradycardia followed by ventricular tachyarrhythmia, with or without hypertension, in the donor dog. A significant increase in the developed tension was observed in the isolated atria, with or without slight sinus acceleration. These effects continued over 150 min after the injection. Digoxin (200 micrograms/Kg, i.v.) caused an immediate bradycardia followed by ventricular tachycardia. In addition, ventricular fibrillation occurred in 3 out of 5 donor dogs within 20 min of the drug administration. In isolated atria, there was a marked increase in the developed tension, usually with a little sinus tachycardia. Deslanoside (200 micrograms/Kg, i.v.) caused almost the same response patterns as digoxin. However, this dose of deslanoside caused ventricular fibrillation in all 6 experiments. Drug concentrations in the donor's arterial blood decreased rapidly for 15-20 min and then decreased slowly in all experiments. It is concluded that digoxin and deslanoside have no significant direct accelerating action on the SA node in doses which produced marked increases in the developed tension; only extremely high doses cause a direct, slight sinus acceleration.