Postischemic myocardial edema depresses left ventricular function and coronary perfusion. Pharmacologic cardioplegia is being used increasingly to enhance myocardial protection during cardiac operations. In the present study we varied the colloid osmotic and osmotic pressures and the infusion pressures of four cardioplegic solutions to determine their respective roles in producing or preventing myocardial edema in a nonischemic setting. We found that myocardial edema during potassium cardioplegia (1) is independent of infusion pressures, (2) is caused by isosmotic crystalloid solutions, (3) is worsened by hyposmolar crystalloid solutions, (4) is avoided by the addition of colloid, and (5) is avoided if the solution is made hyperosmotic with the addition of mannitol.