Antithymocyte globulin (ATG) has been used successfully for induction therapy as well as for treatment of established allograft rejection. However, this therapy has often been associated with problems of overimmunosuppression and increased costs. In a randomized clinical trial, we compared the immunosuppressive benefits, complication rates, and treatment costs when ATG is given as a fixed daily dose or when the dose is adjusted daily according to its biologic effects on T cells. Forty-five recipients of cadaver renal allografts were randomized into two groups. In group 1 (n = 23), ATG (ATGAM) was administered in variable doses to maintain the absolute number of peripheral CD3 T cells at 50-100/microliters. In group 2 (n = 22), ATG was given at a fixed dose of 15 mg/kg/day. All patients received azathioprine and prednisone. ATG was discontinued at 7-14 days when cyclosporine was introduced. In both groups, CD2, CD3, CD4, CD8, and CD19 cells were measured by flow cytometry and the levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, Il-7, and IL-10 were measured by ELISA. In group 2, the levels of all T cell subsets were profoundly suppressed. In group 1, the number of CD3 and other T cells was maintained at about 100 cells/microliters, while the CD19 T cells remained unsuppressed. Cytokine levels were greatly suppressed in group 2 compared with group 1, except for IL-10 levels, which remained elevated in the latter group. Patient survival, graft function, and the incidence of acute and recurrent rejections were similar in the two groups. Bone marrow suppression and infective complications were greater in group 2 than in group 1. The mean daily dose and the total quantity of ATG used in group 1 were significantly smaller than in group 2, resulting in a savings of $2,398.00 per patient per treatment. It is concluded that monitoring of ATG by its biologic effects on T cells is a rational and safe method of regulating the dose of this important agent; in this way, it is possible to reduce the total amount of the drug given to patients with consequent reduction in undesirable complications as well as in the cost of treatment without loss of immunosuppressive benefits.