The action of R56865 has been examined on the contractile effects produced by ouabain concentrations interacting with high (3 microM) and low (300 microM) affinity digitalis receptors on electrically stimulated ventricular strips isolated from rat. R56865 1 microM reduced the increase in resting tension produced by ouabain 300 microM and left unalterated the inotropic effect evoked by ouabain 3 and 300 microM that was reduced by higher concentrations (3 and 6 microM) of R56865. The action of R56865 was also studied on ouabain-induced intoxication in electrically stimulated and spontaneously beating atria of rat. On electrically stimulated (3 Hz) whole atria, R56865 0.3 microM reduced the maximal increase in resting tension produced by ouabain 300 microM and delayed the time to onset of the ouabain-induced arrhythmias but did not affect ouabain's inotropic effect. Higher concentrations of R56865 were required to reduce the inotropic effect of ouabain. The protective action of R56865 against ouabain-induced intoxication was most pronounced on spontaneously beating atria where it reduced spontaneous rate of beats. Experiments in electrically driven left atria indicated that only a part of the protective effect of R56865 could be related to its bradycardic action. The effect of R56865 was also examined on ouabain-induced inhibition of sodium pump in human red blood cells. R56865 6 microM did not modify the inhibition produced by ouabain (from 0.3 to 10 nM), this indicates that the protective action of R56865 against ouabain-induced intoxication is not due to an interaction with the inhibitory effect of ouabain on sodium pump.