A 65-year-old woman was found to have severe autoimmune hemolytic anemia. The patient was group A1, Rho(D) positive. The direct antiglobulin test was strongly positive with anti-C3 and negative with anti- IgG. The serum contained two distinct IgM antibodies, auto-anti-I and auto-anti-AI. Both were reactive at 22 degrees C. However, the anti-AI also was reactive in saline and in albumin at 37 degrees C. An eluate revealed anti-AI and a weak anti-I. Sequential 51Chromium survival studies were done with group OI and AI red cells. The group OI red cells survived normally (97% at 24 hours) while the group A1I red cells were removed in a "two-component" pattern characteristic of IgM complement-fixing antibodies (62% survival at one hour, 49% at 24 hours). Based on these observations, the patient was subsequently transfused without incidence with six group O units of washed red cells prior to splenectomy. Although auto-anti-AI has been previously reported, this is the first case to demonstrate the use of 51Cr survival studies to determine its clinical significance.