SUMMARYThe results of xenogeneic transplantation of tissues in closely related species were compared to those of allografts. A comparative study of transplantation of whole organs, skin grafts, and tritiated thymidine labeled cells into nonsensitized and sensitized recipients was made. Antibody responses were measured. Xenograft and allograft rejection was mediated by cellular mechanisms in nonsensitized recipients. The histologic pattern of rejection was identical. Nonsensitized recipients rejected xenografts slightly faster than allografts. In sensitized recipients, xenografts were rejected wholly by humoral mechanisms, but allografts were rejected both by cellular and by humoral mechanisms. The temporal pattern of rejection was the same in sensitized recipients of allografts or xenografts. In nonsensitized recipients, antibodies to erythrocytes developed more rapidly after xenografting than after allografting, but in sensitized recipients the titers were similar. Cytotoxic antibody was present in sensitized animals that received either xenografts or allografts but the titer was higher in the xenograft recipients. These observations suggest that humoral factors influence the temporal and histologic pattern of rejection. In closely related xenografts, humoral factors are the primary mediators of rejection only after sensitization. However, in sensitized allograft recipients, cellular and probably humoral mechanisms participate.