Autoradiographic studies with 3H-labeled 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] demonstrate, in certain neurons of rat forebrain, hindbrain, and spinal cord, a nuclear retention and concentration of radioactivity, which can be prevented by treatment with 1,25(OH)2D3, but not with 25-hydroxyvitamin D3. These results indicate the presence of brain receptors in addition to pituitary receptors for 1,25(OH)2D3 and suggest a central modulation of calcium homeostasis and other central effects for this hormone. The existence of a brain-pituitary axis for certain 1,25(OH)2D3-mediated endocrine-autonomic effects is postulated.