Epitopes of the 1,25-dihydroxyvitamin D (1,25(OH)(2)D-3) receptor have been shown in developing dorsal root ganglia in fetal mice, as well as in cells maintained in culture [Johnson, J.A., Grande, J.P., Windebank, A.J. and Kumar, R., 1,25-Dihydroxyvitamin D-3 receptors in developing dorsal root ganglia of fetal rats, Dev. Brain Res., 92 (1996) 120-124]. To investigate a possible role for 1,25(OH)(2)D-3 in neural cell growth and development, a murine neuroblastoma cell line that expresses 1,25(OH)(2)D-3 receptors, was treated with 1,25(OH)(2)D-3. Treatment with 1,25(OH)(2)D-3 resulted in a decrease in cell proliferation, a change in cell morphology, and the expression of protein markers of mature neuronal cells. The decrease in cell proliferation was accompanied by an increase in the expression of nerve growth factor (NGF). Anti-NGF monoclonal antibody added to the growth medium blocked the decrease in cell proliferation caused by 1,25(OH)(2)D-3 treatment. Our results show that the sterol hormone 1,25(OH)(2)D-3, causes a decrease in the proliferation of mouse neuroblastoma cells through alterations in the expression of NGF.