Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991). Because receptors for CNTF are expressed in both motoneurons and their target muscles (Davis et al., 1991; lp et al., 1993), both tissues are potential sites of CNTF action in development. We examined the ability of CNTF to prevent the degeneration of a neuromuscular system in developing female rats. The death of motoneurons in the spinal nucleus of the bulbocavernosus (SNB) extends postnatally and is sexually dimorphic, with many more motoneurons dying in females than in males. The bulbocavernosus (BC), a target muscle of SNB motoneurons, also degenerates postnatally in females. Female rats treated with daily injections of 1 microgram CNTF from embryonic day 22 through postnatal day 3 (P3) had 70% more SNB motoneurons on P4 than did control animals, and the number of pyknotic profiles in the SNB area was markedly reduced by CNTF. In addition, the degeneration of the BC was completely prevented by CNTF treatment of perinatal female rats. These results demonstrate that CNTF can preserve mammalian motoneurons from developmental death, but also suggest that the sparing effect of CNTF on motoneurons in vivo may be a secondary consequence of effects on target muscles.