It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion. Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling. The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention. Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared. Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution. Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements. Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01). A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed. The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01). It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant). Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion.