The present study was undertaken to elucidate the potentiation by furosemide of toxicity and positive inotropic effect of ouabain in guinea pigs. Arrhythmogenic responses to ouabain as well as the lowering of its lethal dose were potentiated by pretreatment with furosemide in guinea pigs. The potentiation of ouabain toxicity after furosemide administration was inhibited by pretreatment with potassium sparing diuretic, prorenoate. Furosemide-induced potentiations of contractile force and arrhythmogenic effect of ouabain were also observed in isolated guinea pig papillary muscle. However after pretreatment with furosemide, ouabain produced arrhythmias without any significant changes in either left ventricular or subcellular fractions binding of 3H-ouabain in guinea pigs. These findings suggest that furosemide-induced potentiation of ouabain toxicity is at least in part associated with the decreased intracellular potassium content of guinea pig heart. It was also demonstrated that the positive inotropic action induced by subtoxic dose of ouabain was potentiated by furosemide in guinea pig papillary muscle preparation.