A patient who expired during an episode of gross intravascular hemolysis had a complex medical history, including renal disease, Coombs positive anemia of unclear etiology, recent transfusion, and cholecystectomy. Drug history included 21 different medications, including penicillin, acetaminophen, procainamide, furosemide, sulindac, and tolmetin, all of which have been associated with a positive direct antiglobulin test or drug-induced hemolytic anemia. The patient had a history of recent use of three chemically similar nonsteroidal anti-inflammatory drugs: tolmetin (Tolectin), sulindac (Clinoril), and ketorolac (Toradol). Only tolmetin and furosemide (Lasix) antibodies were demonstrable in the patient's serum at the time of her final admission. The patient's serum at final admission contained panagglutinating IgG and IgM antibody with a titer of 1:80 using a pool of R1R1 and R2R2 screening cells. When tolmetin was added to the test system, the titer increased to 1:2,560. The direct antiglobulin test was 3+ (IgG and C3d,b). Eluates contained an Rh-like antibody compatible only with Rh deletion cells, and anti-tolmetin antibodies detected when the drug was added to the eluate in the presence of Rh deletion cells. Allogeneic adsorbed sera contained anti-tolmetin antibodies with a titer of 1:10 and a weakly reactive IgM antibody to furosemide. Antibodies to tolmetin and furosemide were apparent only when the drugs were added to sera or eluates, not with drug-coated cells. Because of the patient's complex medical history, it was not possible to attribute the fatal autoimmune hemolytic anemia solely to drug antibody.