In the present investigation, the cardiotoxic effects of three anthracycline analogs (doxorubicin, 4'-epi-doxorubicin and 4'-deoxy-doxorubicin) were compared. For this purpose, 9.0 mg/kg of doxorubicin, divided into three closely spaced subdoses, were injected intravenously in rats. The two derivatives were administered according to the same time schedule and their doses were chosen on the basis of the clinically adopted ratio, doxorubicin: 4'-epidoxorubicin: 4'-deoxy-doxorubicin = 1:1:0.5. The degree of cardiomyopathy induced by the three anthracyclines was evaluated by ECG changes and morphological alterations. Doxorubicin was found to produce a significant degree of cardiotoxicity, thus confirming the validity of the experimental model adopted. Both 4'-substituted derivatives proved to be less cardiotoxic than the parent compound, although not completely devoid of this side effect.