AbstractNicorandil, a new antianginal drug, exerts a coronary vasodilation effect by mechanisms different from either nitrates or slow‐channel Ca++entry blockers. This agent has been demonstrated to increase membrane K+conductance, elevate cyclic guanosine monophosphate (GMP) content, and depress Ca++current kinetics in vascular smooth muscle cells. In the myocardium, however, the direct effects of the agent have not been elucidated. We examined whether or not nicorandil could antagonize myocardial injury in the Langendorff‐perfused chick heart induced by the Ca++paradox. The Ca++paradox was produced by 15 min of Ca++‐free perfusion, followed by 10 min of Ca++reperfusion. Nicorandil was added to the perfusing solution only during the Ca++reperfusion phase. In the Ca++paradox hearts, the following were observed: (1) depression of myocardial creatine phosphokinase and adenosine triphosphate (ATP) contents; (2) elevations of myocardial H2O, Na+, and Ca++contents; and (3) ultrastructural derangement, which included contraction bands, interstitial edema, and mitochondrial swelling. Nicorandil treatment significantly attenuated the histological perturbation and part of the biochemical alterations. The present study suggests that nicorandil partially protects the myocardium against the Ca++paradox‐induced