The immune system functions to protect an organism against microbial infections and may be involved in the reparative response to nerve injury. The goal of this study was to determine whether the immune system plays a role in regulating motoneuron survival after a peripheral nerve injury. After a right facial nerve axotomy, facial motoneuron (FMN) survival in CB-17 (/) wild-type mice was found to be 87 3.0% of the unaxotomized left side control. In contrast, facial nerve axotomy in CB-17 (/) severe combined immunodeficient (scid) mice, lacking functional T and B lymphocytes, resulted in an average FMN survival of 55 3.5% relative to the unaxotomized left side control. This represented an 40% decrease in FMN survival compared with wild-type controls. The reconstitution of scid mice with wild-type splenocytes containing T and B lymphocytes restored FMN survival in these mice to the level of the wild-type controls. These results suggest that immune cells associated with acquired immunity play a role in regulating motoneuron survival after a peripheral nerve injury.