Islets of Langerhans treated with donor-specific anti-Ia serum and complement were transplanted across a major histocompatibility barrier into nonimmunosuppressed diabetic mice. The allografts survived in all recipients for at least 200 days after transplantation. Rejection of an established allograft could be induced by intravenous injection of donor splenocytes. This demonstrates that allografts can serve as targets for immune rejection and supports the possible role of Ia-positive passenger lymphoid cells in initiation of immune rejection. The results show that immunosuppression of the recipient is not a prerequisite for successful transplantation.