After heart transplantation, right ventricular failure can occur because of increased afterload. Previous studies have suggested that the maximal pressure the right ventricle can develop is determined primarily by right ventricular perfusion pressure. However, the interaction of the left ventricle and the pericardium as functional co-determinants of maximal right ventricular function is unknown. This study was undertaken to determine the interaction of the pericardium, left ventricular pressure, and right coronary artery perfusion pressure as potential determinants of maximal right ventricular function. In an acute canine preparation, with progressive pulmonary artery constriction, maximal generated right ventricular pressure was determined over a range of left ventricular systolic pressures. Additional groups of dogs were studied with the right coronary artery cannulated and were maintained at constant perfusion pressure. In all preparations, the maximal pressure the right ventricle could generate was linearly related to left ventricular systolic pressure. Having a closed pericardium markedly enhanced this effect; some effect was present with an open pericardium, although the magnitude of the influence of left ventricular pressure on maximal right ventricular pressure was much less. Maintaining constancy of right coronary artery perfusion pressure, either at high or low values, did not alter these findings nor did it alter the influence of the pericardium. These results suggest that right ventricular perfusion may not be the sole determinant of maximal right ventricular function. Furthermore, with the pericardium open, such as in the posttransplantation state, the left ventricular contribution to maximal right ventricular function may be diminished, increasing vulnerability for right ventricular failure caused by increased afterload.