Heart transplant patients who develop early (within 2 weeks after transplantation) severe renal dysfunction require an alternative to cyclosporine-based immunosuppressive induction therapy. In our experience, muromonab-CD3 (Orthoclone OKT3) is an excellent alternative for such patients. When compared with cyclosporine, however, it is associated with a higher incidence of infection. We conducted a retrospective analysis of a series of our patients to improve our ability to identify such patients. Selected risk factors for severe renal dysfunction included creatinine clearance less than 55 ml/min, hospitalization before transplant, perioperative cardiovascular compromise, and mechanical circulatory support. Of 50 adult patients (mean age 52 years), 35 (70%) completed full induction with intravenous (IV) cyclosporine (1 to 4 mg/kg/24 hr); 13 (26%) developed severe renal dysfunction; and two (4%) were excluded as a result of nonprotocol failures. Of the 13 patients in whom IV cyclosporine induction was precluded by severe renal dysfunction, 11 (85%) received IV OKT3 (5 mg/24 hr), and two (15%) received antithymocyte globulin (14 mg/kg/24 hr). Chi-square analysis showed perioperative cardiovascular compromise (p less than 0.001), hospitalization before transplant (p less than 0.001), and low creatinine clearance level (p less than 0.01) to be significantly associated with the development of severe renal dysfunction. The incidence of infection among patients treated with only IV cyclosporine versus OKT3 was 0.7 and 2.3 episodes per patient, respectively. This experience suggests that the selective use of OKT3 and IV cyclosporine with the use of risk factor analysis may improve individualization of induction therapy in heart transplant patients.