Streptozotocin-induced diabetes in mice can be reversed by transplantation of islets of Langerhans from histoincompatible mice if the islets are treated with anti-Ia-serum and complement before transplantation. Here we show that anti-Ia-treated islets most likely induce tolerance in the recipient animals. Daily injections of recipient-specific anti-I-J-serum (beginning 80 or more days after transplantation) and small numbers of donor splenocytes caused the prompt rejection of the islets in half of the animals; neither anti-I-J-serum nor donor splenocytes alone were effective. It is likely that rejection of established allografts after this treatment is the result of abolition of the activity of allograft-specific suppressor cells.