OKT3 antibody therapy is effective in the treatment of renal allograft rejection. However its exact mode of action is unknown. Following OKT3 administration, peripheral blood lymphocytes fail to express the CD3 antigen, although other membrane antigens are relatively preserved. In this way the lymphocytes are unable to respondtoforeign antigens. It is not known whether this modulation of CD3 on lymphocytes occurs within the rejecting allograft. Ten patients who received OKT3 therapy for steroid-resistant renal allograft rejection were studied. The aim of the study was to examine whether OKT3 antibody therapy altered the degree or the relative composition of the inflammatory infiltrate and to assess whether 0KT3 treatment resulted in modulation of CD3 on intragraft lymphocytes. The study involved immunoperoxidase examination of biopsy material and flow cytometric analysis of peripheral blood lymphocytes obtained before and during treatment with OKT3 antibody. The results show that the total number of infiltrating leukocytes decreased after 5 days of treatment (3215±700 cells/1. 0 mm2of tissue before vs. 1730±635 at day 5; P < 0.001). The relative proportions of macrophages, total lymphocytes, CD4 +ve and CD8 +ve cells did not alter during therapy. Despite marked modulation of peripheral blood lymphocytes (CD3/CD2 ratio 0.89±0.13 before vs. 0.10± 0.11 during treatment,P< 0.001), there was no evidence of modulation of intragraft lymphocytes (CD3/CD2 ratio 0.98± 0.14 before vs. 0.90±0.21 during treatment, P=NS). Although OKT3 antibody therapy is effective clinically at improving renal allograft rejection, this study demonstrates that it does not appear to cause modulation of the CD3 antigen on intragraft lymphocytes.