Abstract. Of 71 patients showing a negative direct antiglobulin (Coombs‘) test (DAT) before administration of cephalexin (CEX) three developed a positive DAT after therapy with this drug (4%). No case of immunohemolytic anemia was observed. The sera of the patients with a positive DAT reacted with cephalothin‐coated red cells producing high titers, with penicillin cells normal titers and with CEX cells low titers. Since the red cell eluates of these patients did not give significant reactions with red cells sensitized with CEX, cephalothin and penicillin, a nonimmunological mechanism for the development of the positive DAT in these patients has to be assumed.