The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.