When motoneuron axons in peripheral nerves are injured, the expression of the p75 low-affinity neurotrophin receptor (p75) increases in their cell bodies and axons, as well as in the Schwann cells undergoing Wallerian degeneration in the distal excised nerve segment. To understand the role of p75 in the events following nerve injury, we have examined the survival and regeneration of motoneurons in mice lacking the p75 receptor. In adult p75 (-/-) mice, functional recovery of whiskers movement following a facial nerve crush occurred slightly earlier than in p75 (+/+) mice, and some recovery of function over a 25-day interval following a nerve cut occurred more frequently in p75 (-/-) mice. Motoneuron profile numbers were slightly reduced in p75 (-/-) mice, and there were correspondingly fewer axons in the facial nerve. At 25 days following axotomy, profile survival in the adult p75 (-/-) mice was significantly improved compared to p75 (+/+) mice (mean 85%+/-standard error of the mean 3%, n = 11 vs. 67+/-5%, n = 11 in CD-1 mice and 68.0+/-4%, n = 6 in balb/c mice), and significantly more regenerating axons were present in the distal facial nerve. After axotomy on postnatal day 1, there was almost total loss of motoneuron profiles in the lateral facial nucleus in p75 (+/+) mice (1.7+/-0.3% remained, n = 5), while significantly more survived in p75 (-/-) mice (17 +/-2.5 %, n = 6). We conclude that expression of p75 in motoneurons or Schwann cells following facial nerve injury is not necessary for motoneuron survival or prompt regeneration of their axons; rather, p75 may increase their risk of dying.