✓ Schwann cells survive longer in allografts of ganglia that contain minor, rather than major and minor, transplantation antigens. The authors have investigated whether a nerve allograft with minor antigens would be superior to one with major and minor incompatibilities in aiding in the repair of injured nerve. A segment of host peroneal nerve was removed from rats and replaced with a peroneal nerve allograft that contained either minor or major and minor antigens. The results showed that in normal rats, host nerve fibers could functionally regenerate through (that is, grow through and reinnervate muscle) nerve allografts 2 cm but not 4 cm in length, irrespective of the antigens the allografts contained. Host nerve fibers could, however, regenerate through 4-cm nerve allografts if the hosts were rendered immunologically tolerant of the transplantation antigens of the nerve donors. Furthermore, when sensitized lymphoid cells were injected into tolerant rats bearing functional nerve allografts, Schwann cell rejection and demyelination occurred in the graft but host nerve fibers remained. It is concluded that minor antigens alone are as potent as major and minor antigens together in evoking an immune response that prevents functional regeneration through long lengths of nerve allografts. Host nerve fibers can, however, regenerate through such nerve allografts if the hosts are immunosuppressed.