An 80-year-old group O, D- (rr) female with anti-C, -D, -E, and -Fya received four units of crossmatch-compatible red blood cells (RBCs). The direct antiglobulin test (DAT) was negative. Two weeks later, jaundice, dark urine, a 16% drop in hematocrit (Hct), a 20% reticulocyte count, and absent haptoglobin occurred. During the next month, her DAT was positive with anti-IgG and -C3d. Acid eluates, which repeatedly showed anti-D specificity, were nonreactive with enzyme-treated D- RBCs. Adsorption with D- RBCs reduced reactivity. An eluate from the adsorbing D- RBCs was nonreactive with D+ KBCs. These findings suggest an autoantibody mimicking alloanti-D. The patient was treated with prednisone and was transfused with group O, D- (rr), K-, Fy(a-) RBCs. Four months later, the Hct was stable. One year later, the DAT remained positive and the eluate demonstrated a panagglutinin.