BACKGROUND Administration of aprotinin during extracorporeal circulation reduces blood loss and improves platelet function. RESULTS To evaluate the protective effect of aprotinin on platelets, 50 patients undergoing cardiopulmonary bypass were randomized before surgery to one of three groups. Seventeen patients (group A) received continuous high-dose aprotinin (7 x 10(6) KIU) during cardiopulmonary bypass, 17 (group B) received a single bolus of aprotinin in the pump prime (2 x 10(6) KIU), and 16 (group C) received placebo. Scanning electron microscopy was used to evaluate platelet aggregation on extracellular matrix. The platelet function was graded from 1 to 4, with grade 4 being normal aggregation. Immediately after cardiopulmonary bypass, 16 patients in group A (94%) reached preoperative aggregation grade (mean grade, 3.4 +/- 0.7) compared with nine of 17 in group B (52%) (mean grade, 2.9 +/- 1.2), and none in group C (0%) (mean grade, 1.4 +/- 0.5; p < 0.001). Postoperative platelet count did not differ significantly among the three groups. After surgery, group A bled less than groups B and C (395 +/- 120 versus 488 +/- 135 and 780 +/- 408 ml, respectively; p < 0.01). Patients in the aprotinin groups received fewer red blood cell units (0.9 +/- 1.2 and 1.9 +/- 1.2 versus 3.4 +/- 1.9, respectively; p < 0.01) and were exposed to less homologous blood products (1.3 +/- 1.7 and 2.1 +/- 1.1 versus 6.1 +/- 5, respectively; p < 0.001). CONCLUSIONS By preserving platelet function, aprotinin improves postoperative hemostasis in all patients who receive high dose and in most who receive low dose.