Despite incontrovertable evidence demonstrating the unique immunosuppressive capabilities of antihymocyte globulin (ATG) in animals, its value in clinical transplantation has remained inconclusive. A multicenter, prospective study was undertaken in an attempt to determine this value. Cadaver renal allograft recipients were randomized into two treatment groups: prednisone and azathioprine only, or prednisone, azathioprine, and ATG. Four to 36 month follow-up of our first 50 recipients, supported by results in over 200 patients from other centers, permits the following observations. (1) Allograft survival can be improved by nearly 20 percent in recipients treated with active ATG preparations. (2) Presently available assays performed in vitro and on subhuman primate allograft survival, though capable of excluding inactive preparations, cannot quantitate precisely the immunosuppressive capacity of active batches of ATG. (3) Monitoring circulating T cell levels in patients receiving ATG appears to offer the best means of defining immunosuppressive potency and the variation in response to the agent among identically treated individuals. It is concluded that ATG therapy can be beneficial in renal transplantation; but monitoring of recipients' T cell level is desirable during therapy to determine the dosage required. Furthermore, the optimal immunosuppressive protocol can be approximated by modifying the regimen according to individual variations in response, thus limiting the infectious complications of excessive immunosuppression.