The capacity of facial motor neurons (FMN) to survive injury and successfully regenerate is substantially compromised in immunodeficient mice, which lack T and B lymphocytes (). The goal of the present study was to determine which T cell subset (CD4+ and/or CD8+), and whether the B lymphocyte, is involved in FMN survival after nerve injury. All mice were subjected to a right facial nerve axotomy, with the left (uncut) side serving as an internal control. FMN survival, of the right (cut) side, was measured 4 weeks post-operative, and expressed as a percentage of the left (uncut) control side. FMN survival in wild-type mice was 86%+/-1.5. In contrast, FMN survival in CD4 KO mice was 60%+/-2.0. Reconstitution of either CD4 KO mice, or recombinase activating gene-2 knockout (RAG-2 KO) mice (which lack functional T and B cells) with CD4+ T cells alone restored FMN survival to wild-type levels (85%+/-1.2 and 84%+/-2.5, respectively). There was no difference in FMN survival between wild-type, CD8 KO and MmuMT (B cell deficient) mice. Reconstitution of RAG-2 KO mice with CD8+ T cells alone, or B cells alone, failed to restore FMN survival levels (65%+/-1.5 and 63%+/-1.0, respectively). It is concluded that, of the population of FMN that do not survive injury, CD4+ T lymphocytes, but not CD8+ T lymphocytes or B cells, mediate FMN survival after peripheral nerve injury.