Motoneuron development was studied in the spinal cord of the mouse mutant, muscular dysgenesis, between embryonic days (E) 13 and 18. Dysgenic embryos are characterized by the absence of neuromuscular activity (motility) and exhibit a number of other striking changes in neuromuscular development. Many of these changes have also been observed in chick embryos chronically treated with neuromuscular blocking agents that suppress motility. Motoneuron survival, as well as several other aspects of neuronal development, was examined in the thoracic and lumbar spinal cords of mutant and control embryos. There was a significant decrease in motoneuron numbers in control embryos indicating the presence of naturally occurring cell death in the mouse spinal cord. At all ages examined, the dysgenic embryos had significantly more healthy and significantly fewer degenerating motoneurons than controls. There were no differences in the number of dorsal root ganglion neurons or in any of the other morphometric parameters examined between mutant and control embryos. Creatine kinase activity, a marker for myofiber maturation, was significantly reduced in the limb musculature of mutant embryos. Choline acetyltransferase activity was significantly increased in the spinal cord of mutant embryos. No significant differences were observed in spinal cord levels of acetylcholinesterase activity between control and mutant embryos. The absence of muscle contractions in the dysgenic mouse is associated with a number of changes in neuromuscular development, including a substantial reduction of naturally occurring motoneuron death.