Twenty-six rhesus monkeys were paired on the basis of RhLA serologically defined (SD) antigens and then mixed lymphocyte cultures (MLCs) were performed for each donor-recipient combination. All but one monkey responded positively to its partner in MLC. In vitro assays for complement-dependent antibody-mediated cytotoxicity (CDC) and lymphocyte-mediated cytotoxicity (LMC) were performed before and after each of two separate orthotopic tooth transplants for each recipient. There was no detectable CDC or LMC before tooth transplantation. The maxillary right central incisors were exchanged between paired monkeys and 60 days later the left maxillary central incisors were transplanted. After the first tooth allograft, there was very little CDC activity in any recipient and only one matched group showed any remarkable LMC activity. However, after the second tooth transplant there was a very clear CDC response in the majority of monkeys. The LMC activity remained low after retransplantation. There did not seem to be any consistent relationship between RhLA match and in vitro cytotoxicity. The results indicate that tooth allografts are weak immunogens but they do evoke humoral immunity after retransplantation. The biological relevance of these serum antibodies remains to be determined.