To investigate retrograde delivery of cardioplegic solutions as a means of enhancing myocardial protection in the presence of coronary artery occlusion, a two-part experimental model was devised. In part 1 (in vitro) the possibility of retroperfusing the entire myocardium during acute occlusion of the left anterior descending artery (LAD) was assessed. In part 2 (in vivo) acute LAD occlusion was performed in dogs, and during 2 hours of aortic cross-clamping crystalline cardioplegic solution was infused at 20-minute intervals. In group I the infusion was antegrade, via the aortic root, and in group II it was retrograde, via the coronary sinus. Thereafter the LAD snare was released and the dogs were weaned from bypass. Delivery of cardioplegia through the aortic root was associated with depression of ventricular function, poor myocardial cooling and severe cellular damage. With the retrograde procedure there was significantly improved recovery of left ventricular function, uniform myocardial cooling and better preservation of cellular morphology.