Conventional blood conservation techniques have been insufficient to decrease transfusion needs in increasingly complex cardiac operations. To evaluate combinations of conservation techniques, 300 patients were divided into three equal groups. Group 1 had intraoperative autotransfusion and return of mediastinal drainage for 4 hours postoperatively. Group 2 had these measures plus intraoperative plasmapheresis. These two groups were given a transfusion for a hematocrit of less than 0.21 on cardiopulmonary bypass. Group 3 was treated with the same measures as group 2 but did not receive transfusions while on pump unless the hematocrit decreased to less than 0.15. The percentage of patients in each group given transfusions in the operating room was 34% in group 1, 28% in group 2, and 7% in group 3 (p less than 0.05). The percentage of all patients receiving transfusions during hospitalization was 68% in group 1, 36% in group 2 (p less than 0.05), and 18% in group 3 (p less than 0.05). Average total units transfused were 2.16 +/- 0.25 in group 1, 0.7 +/- 0.15 in group 2 (p less than 0.05), and 0.37 +/- 0.07 in group 3 (p less than 0.05). The perioperative morbidity rates including myocardial infarctions and strokes were similar. There were no deaths in group 3. Combining complementary conservation measures is effective in reducing homologous blood transfusions, and the need for transfusion can be safely reduced by allowing profound hemodilution during bypass.