Human fetal splenocytes were isolated, labeled with 51chromium, and transfused into NOD male mice for determination of cell survival. One-half of the mice received splenocytes which had been incubated in cyclosporine A (CSA, 20 micrograms/ml) for 30 min and washed extensively, while controls received splenocytes incubated in diluent alone. After the first transfusion of splenocytes, survival was the same for both CSA-treated and control animals with a t 1/2 of 34 days. A second survival study showed a decrease of t 1/2 in the control animals to 18 days and an increase in the animals receiving CSA treated cells to 53 days (P less than 0.01). These in vivo studies confirm in vitro studies documenting that pretreatment of donor cells with CSA is an effective means of modulating the immune response.