The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action.