In the 1970s, the most common causes of drug-induced immune hemolytic anemia were methyldopa and penicillin. Since 1990, the most common causes of drug-induced immune hemolytic anemia have been the second- and third-generation cephalosporins, cefotetan and ceftriaxone. Three case histories illustrate the common findings in the serologic investigation of immune hemolytic anemias due to these two drugs.