The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same 51Cr-labeled red cells followed by the transfusion of the remainder of the red cell unit. The long-term T 1/2Cr survival for each case was patient 1 (anti-McCa), 15 days; patient 2 (anti-JMH), 12 days; patient 3 (anti-Kna), 31 days; patient 4 (anti-McCa), 12 days; and patient 5 (anti-Hya), 14 days. Each antibody tested in an in vitro homologous macrophage assay showed less than 5 percent phagocytosis. Anti-JMH was the only antibody to react with IgG subclass antisera and was determined to be IgG4. The macrophage assay, IgG subclass testing, and short-term (1 hour, 1 ml) 51Cr survival studies all indicated that the short-term survival was good. However, only the measurement of long-term survival with transfused units of serologically incompatible red cells was able to determine the actual survival, and "clinical significance" of the alloantibodies. Determining the actual long-term survival by the method described here can be of importance for patients requiring chronic red cell transfusion.