We compared the infections eccouraged in 23 renal transplant patioents given the monclonical anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of staroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factore predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclop9oraine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection eposode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 epidodes vs. 4, P=.02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)—Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cyutomegalovirus (CMV) pneumonia (1), Yersina infection with severe dermatophytosis (1). adn Epstein-Barr virus-associated lymphoproliferative syndrome (1)—as compared with 1 case of mild CMV infection in the control group (P=.08). Trimethoprimsulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis adn M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejecion in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-meiodated immunity. Prophylaxis with TMP-SMZ, which is sage, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may ne especially important during OKT3 therapy.