Calcitonin gene-related peptide (CGRP) is found in motoneurons of the mammalian spinal cord, including motoneurons of the androgen-dependent spinal nucleus of the bulbocavernosus (SNB) of the mouse. Motoneurons of the SNB innervate the bulbocavernosus (BC), a striated muscle involved in penile reflexes. CGRP is though to be a trophic factor produced by motoneurons to regulate the expression of the acetylcholine receptor at the neuromuscular junction. In rats, the number of SNB motoneurons containing CGRP is increased by gonadal steroids. This regulation appears to rely on an activity-dependent factor produced by the BC muscle. The purpose of the present study was to examine, using immunohistochemistry, the steroid dependence of CGRP in the SNB of male house mice. Genotypic differences in the steroid regulation of CGRP immunoreactivity were examined in three strains of mice that differ in their behavioral sensitivity to castration. The results demonstrate that castration reduces the number of CGRP-positive SNB motoneurons in mice. The magnitude of the change in CGRP in response to castration and the length of time required following castration to alter CGRP were dependent on genotype. Interestingly, the effect of castration in mice, to reduce the number of CGRP-immunoreactive SNB motoneurons, is opposite in direction from the increase in CGRP SNB motoneurons observed in rats observed following castration. These experiments suggest that androgens may alter neuromuscular junction function of mouse SNB by regulating the production of CGRP in a species-specific, genotypically dependent fashion.