Everolimus (rapamycin derivative, RAD) is a new immunosuppressive drug that prevents allograft rejection. Herein, the pharmacodynamics of everolimus in human renal-allograft recipients is evaluated. Single doses of everolimus (0.75–10 mg), combined with a maintenance immunosuppressive therapy based on CyA, decreased lymphocyte proliferation. In addition, the effect of multiple doses of everolimus (0.75–10 mg) given daily for 21 days, to stable renal-allograft patients (n = 11), was investigated. Everolimus treatment resulted in immediate inhibition (25–55%) of lymphocyte proliferation in renal-allograft recipients; values returning to baseline by 14 days after cessation of everolimus treatment. Placebo-treated patients showed no decrease in lymphocyte proliferation. Interestingly, everolimus reduced IL-10 synthesis by 20–60% in renal-allograft recipients. Phagocytosis rates were not changed by everolimus. In vitro, everolimus inhibited lymphocyte proliferation and IL-10 synthesis dose dependently in anti-CD3 mAb and LPS stimulated peripheral blood mononuclear cell cultures derived from human volunteers.