We previously reported that ultraviolet-B-irradiated B10.AQR tail skin grafts were permanently accepted by B10.T6R recipients in about half the cases. Such a beneficial effect on graft survival could only be demonstrated in this particular combination. We have now investigated whether these animals had become tolerant to the donor strain antigens. Nonirradiated B10.AQR tail skin grafted 50 days after acceptance of a UVB-irradiated B10.AQR graft was accepted in 9/9 cases, indicating that these animals had become tolerant to the B10.AQR alloantigens. However, secondary grafts on animals that had rejected the first graft also showed a prolonged or definite survival. This tolerance was specific; B10.T6R mice tolerant to B10.AQR grafts rejected B10 skin grafts, while F1(B10A X B10.AQR) and F1(B10 X B10A) grafts, sharing class II antigens with B10.AQR, had a slightly prolonged graft survival. Cells of tolerant animals showed normal proliferative responses against B10.AQR antigens. However, when autologous serum was added, proliferation was specifically suppressed. Likewise, this specific tolerance could be transferred with serum or serum and cells but not with cells only. Analysis of the sera of these animals showed long-lasting and donor-specific high-titered cytotoxic antibody titers, which are likely to play a pivotal role in the observed suppression.