Rat pregnancy, experimental pseudopregnancy, and experimental decidua induction promote skin allograft survival of paternal and unrelated skin donors by specific and nonspecific mechanisms. Experimental pseudopregnant females were given allogeneic cells by two routes: intraperitoneal (IP) and in utero (IU). The females injected by the IU route, with allosensitized spleen cells, tolerated paternal skin allografts (average 26 days) better than those from other experimental groups and even from allopregnant females bearing a paternal allograft. The orthotopic immunization by the IU route, as shown by an enhancing effect of in utero culture medium injection, seemed important. In vitro studies revealed that the ability of subscapular lymph node (SCLN) cells draining the allograft to destroy Wistar/Furth (W/Fu) target cells decreases markedly in parallel with prolongation of skin allograft survival. Suppression of lymphocyte-mediated cytotoxicity against W/Fu target cells exceeded 70% when SCLN cells were used as responder cells. We propose that maternal T-cell immunization (via in utero) against fetal antigens occurs in pregnancy and plays a role in maintaining fetal tolerance, while specific cell-mediated cytotoxicity is impaired. Both specific and nonspecific local factors may promote such an enhancement of allograft survival.