We have investigated in a prospective, randomised placebo-controlled study the effect of high-dose aprotinin on blood loss in patients admitted for major surgery (revision arthroplasty of the hip or knee, or for resection of a soft-tissue sarcoma). The mean intraoperative blood loss was reduced from 1957 ml in the control group to 736 ml in the aprotinin group (p = 0.002). The mean requirement for intraoperative homologous blood transfusion in the aprotinin group was 1.4 units (95% CI 0.2 to 2.7) and 3.1 units (95% CI 1.7 to 4.6) in the control group (p = 0.033). The mean length of hospital stay was reduced from 27.8 days in the control group to 17.6 days in the aprotinin group which was not statistically significant. The intraoperative use of aprotinin in major orthopaedic operations significantly reduced blood loss and the required amount of packed cells. It may result in a decrease in the length of hospital stay and costs