Abstract: Parental-to-F 1 -hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F 1 recipients demonstrate an immunological response to the parental graft. Female F 1 recipients, particularly those carrying the H-2 b haplotype, respond vigorously to male parental liver grafts. However F 1 female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F 1 females as long as the F 1 carries the H-2 b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F 1 and C3H.SW animals, a response which is absent in C3H females. Female F 1 hybrids carrying the H-2 b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F 1 response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F 1 hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (OH x B6 or B10) F 1 hybrids.