OKT3 induction therapy was monitored in 31 cardiac allograft recipients during the Ist year posttransplant. Serum level of OKT3, anti-OKT3 antibodies, and interleukin-2 (IL-2) were monitored during the first 2 months posttransplant. These values were retrospectively correlated with allograft rejection episodes which occurred during the Ist year posttransplant and allograft survival rates over a 3-year observation period. We found that OKT3 induction therapy (10-14 days) was not associated with the development of anti-OKT3 antibodies manifest by dropping OKT3 levels during OKT3 therapy, and is not associated with the development of vascular rejection in our patient population. Patients with high titer ant-OKT3 antibodies, erratic serum OKT3 levels, and/or high serum IL-2 levels (greater than or equal to 5 ng/ml) during the first 2 months posttransplant showed a higher incidence of allograft rejection (predominantly cellular rejection) during the Ist year posttransplant and showed lower allograft survival rates. We also showed that a concomitant elevation of serum IL-2 levels was found in patients who developed anti-OKT3 antibodies. CD3(+) T-cell levels were not predictive of inefficacy of OKT3 therapy. We conclude that immunologic monitoring of serum OKT3, anti-OKT3 antibody, and possibly serum IL-2 levels is critical for identification of patients who develop early, OKT3-resistant rejection episodes and for the identification of patients who may be more susceptible to allograft rejection and decreased allograft survival long after completion of OKT3 therapy.