OBJECTIVE--To determine whether two low dose aprotinin regimens produce clinically significant reductions in postoperative blood loss compared with a control group. DESIGN--A randomised double blind placebo controlled study. SETTING--A regional cardiothoracic unit in London. PATIENTS--79 patients were consecutively allocated to one of three groups. All patients had primary elective surgery with standard anaesthetic and surgical techniques, and no patients were withdrawn from the study. INTERVENTIONS--Group K patients (n = 27) received aprotinin (10(6) kallikrein inactivator units (KIU) into the pump prime whereas group L patients (n = 27) received an intravenous bolus of aprotinin (0.5 x 10(6) KIU) after induction of anaesthesia and 10(6) KIU was added to the pump prime. A third group (group J, n = 25) received 0.9% saline placebo. MAIN OUTCOME MEASURES--After insertion of the chest drains at the end of cardiopulmonary bypass, blood losses were measured hourly until the drains were removed 18 to 24 h later. Total haemoglobin loss into the chest drains was calculated. RESULTS--Both aprotinin treated groups showed significantly less postoperative blood loss than controls (medians: group K, 400 ml; group L, 400 ml; v controls 780 ml; p < 0.001) and there was even less measured postoperative haemoglobin loss within the chest drains in both the aprotinin treated groups than in the controls (medians: group K, 16 g; group L, 19 g; v controls, 47 g; p < 0.001). CONCLUSION--In primary cardiac surgery the dose of aprotinin may be reduced by about 80% from the recommended high dose schedule and still significantly reduce postoperative blood loss compared with placebo.