A patient who developed an autoimmune hemolytic anemia during treatment with ibuprofen (Motrin) is described. Positive indirect Coombs' reaction was demonstrated with the patient's red blood cell eluate in the presence of the drug, supporting a drug-related immune hemolysis. The positive direct Coombs' reaction to anti-C3 antiserum strongly suggested that the immune hemolysis in this patient is probably mediated through complement alone; however, the presence of a small amount of IgG antibodies on the surface of the red blood cells which cannot be detected under conventional screening procedures cannot be completely excluded. Further studies, both clinical and laboratory, disclosed that the responsible ingredient in this particular instance appeared to be the orange dye coating of the Motrin-400 tablet rather than the ibuprofen itself.