27 skin allografts were transplanted in duplicate to 13 rabbits defective in the sixth component (C'6) of complement (C'). 14 were rejected within the normal period of time and 9 only after a significant delay. In four grafts, no rejection was observed. Grafts exchanged between C' active and C' defective littermates tended to persist viable longer on the C' defective partners.
It is concluded that in a species of higher vertebrates, the rabbit, allograft rejection can proceed in the absence of C'6 and the biological functions depending on it. This includes the cytotoxic function of complement. However, the prolonged survival in C'6 defective rabbits of some allografts strongly suggests that two pathways may be operative in the rejection reaction. The results are consistent with the view that a mechanism independent of C'6 was alone fully effective in the majority of the donor-host combinations. A C'6-dependent mechanism became influential only in some specific donor-host combinations.