To determine if the myocardial protection afforded by a cold crystalloid potassium cardioplegic solution could be improved by the addition of either mannitol or albumin, a prospective clinical study was undertaken in which 58 patients undergoing elective aortocoronary bypass were randomized to one of three groups. Each group featured a different cardioplegic solution. The solutions were a standard potassium crystalloid solution, a solution containing mannitol sufficient to raise the osmolality by 20 to 30 mOsm, and a solution containing 5% albumin. Preoperative, intraoperative, and postoperative evaluation included serial measurements of ejection fraction, myocardial-specific isoenzyme, and hemodynamic indexes of performance. Electrocardiographic evaluation for perioperative myocardial infarction and the need for postoperative inotropic and mechanical support were also included. No differences were found among the groups. Therefore, although the use of mannitol or albumin has been shown to be beneficial in an experimental setting, superiority of either additive could not be demonstrated clinically.