The use of the monoclonal antibody OKT3 for induction immunosuppression in renal transplantation is increasing—however, the safety of intraoperative administration continues to be questioned because of first-dose effects. The current study was designed to examine the effects of intraoperative administration of OKT3 on the cardiovascular and pulmonary systems in 161 consecutive renal transplant recipients. Patients receiving OKT3 intraoperatively during renal transplant (99 cadaver recipients) were compared with 62 patients not administered the drug (31 cadaver, 25 living-related-donor, 6 living-nonrelated donor). Intraoperative airway pressure (highest, average), O2 saturation (SaO2), temperature, blood pressure changes, cardiac rhythm, and bronchospasm were compared in these two groups. Significant physiologic changes noted in the group receiving OKT3 included increased temperature (both in-traoperative and postoperative), decreased SaO2 (postoperative), and increased FiO2 (postoperative). Despite these differences, no clinically significant changes were noted in the group receiving OKT3. OKT3 induction given at the time of surgery was associated with a significantly increased one- and three-year graft function. This study demonstrates that first-dose administration of OKT3 intraoperatively during renal transplantation is safe and effective.