Androgens can rescue axotomized motor neurons from cell death. Here we examine a possible mechanism for this trophic action in juvenile Xenopus laevis: regulation of a calcium-binding protein, calbindin, after axotomy. Western analysis revealed that a monoclonal antibody to calbindin D specifically recognizes a single approximately 28 kDa band in X. laevis CNS and rat cerebellum. Retrograde transport of peroxidase combined with immunohistochemistry demonstrated that somata, axons, and synaptic terminals of laryngeal motor neurons in nucleus (N.) IX-X of X. laevis are calbindin-positive. The number of calbindin-positive cells was compared in the intact and axotomized sides of N.IX-X of gonadectomized males that were either hormonally untreated or DHT-treated for 1 month. Although axotomy decreased the number of calbindin-positive cells by 86% in hormonally untreated males, the decrease was only 56% in DHT-treated animals. Compared with hormonally untreated animals, the number of calbindin-labeled cells in N.IX-X of DHT-treated males was increased in both the intact (14%) and axotomized sides (75%). We conclude that axotomy decreases and that DHT enhances calbindin immunoreactivity in N.IX-X. Axotomy-induced decrease in calbindin immunoreactivity precedes cell loss in N.IX-X and may impair the capacity of motor neurons to regulate cytoplasmic calcium. Androgen-mediated maintenance of calbindin expression is thus a candidate cellular mechanism for trophic maintenance of hormone target neurons.