SUMMARYElectrolytic lesions were produced in the tuberal hypothalamus and amygdala of male Fischer and female BNLF1rats, and in male Fischer and female BNLF1rats that had received antecedent hypophysectomies. Skin grafts from Lewis rats survived less well on tuberal-lesioned male Fischer rats than similar grafts on sham-operated and amygdala-lesioned male Fischer rats. Lewis skin graft survival was also curtailed in male Fischer rats that had received hypophysectomies followed by tuberal lesions. These differences were not apparent across the male to female (H-Y) BNLF1histocompatibility barrier.We conclude: (1) that tuberal hypothalamic lesions stimulate allograft reactivity in rats, (2) that this response is greater when the immunogenetic disparity between donor and host is greater, and (3) that the mechanism governing this response involves a direct neural pathway which bypasses the hypothalamic-hypophyseal axis.