The effects of ASI-222 HCl and digoxin on cardiac contractile force, dP/dt, heart rate and mean blood pressure in the dog were evaluated following i.v. administration. Additional studies were performed on isolated, electrically driven rabbit atria with both ASI-222 and digoxin. Our data show that ASI-222 (40 microgram/kg) in non-vagotomized dogs produced a two-fold greater increase in cardiac contractile force and dP/dt than did an equimolar dose of digoxin. ASI-222 caused a peak increase in contractile force and dP/dt 10 min after administration, whereas the peak to digoxin occurred at 30 min. ASI-222 was more effective in non-vagotomized dogs in increasing contractile force and dP/dt than in vagatonized dogs. The inotropic responses to digoxin were not reduced by vagotomy. Studies on isolated electrically driven rabbit atria indicate ASI-222 to be 7-8 times more potent than digoxin in increasing contractile force. These data demonstrate that ASI-222 produces an earlier and greater increase in contractile force and dP/dt than digoxin in equimolar doses.