Four mule foals received anti-RBC antibody from their dam's colostrum. Two foals developed anemia, 1 developed severe thrombocytopenia, and 1 did not develop any clinical or laboratory abnormalities. All foals had the same donkey sire. Seven mares, including the dams of foals 1 to 4, bred to the donkey sire produced anti-RBC antibody. Two mares produced anti-RBC antibody to the donkey RBC on the first mating. The donkey sire and 18 of its offspring were found to have an RBC antigen unique to mules and donkeys. Thus, all matings of this donkey to horse mares were incompatible. The reason for the high rate of sensitization of mares bred to this donkey is unknown.