ABSTRACT The techniques of total body neutron activation analysis and whole body counting were utilized to examine the effect of hypercortisolism on skeletal mass and body composition. Eight patients with Cushing's syndrome were studied. In addition, serum concentration of 25-hydroxycholecalciferol was measured in 4 of these patients, and in an additional 17 patients who were receiving exogenous glucocorticoids. Prior to therapy, skeletal mass (total body Ca) and lean body mass (40K) were considered to be decreased in 5 out of 7 patients. The osteopenia was generally not corrected in follow-up activations subsequent to treatment of the Cushing's syndrome. The only significant increases in total body calcium occurred in 2 patients who presumably had not completed body growth. Serum levels of 25-hydroxycholecalciferol were in the normal range in the spontaneous Cushing's, as well as the iatrogenic Cushing's syndrome patients. Thus, if glucocorticoids affect vitamin D metabolism, it must be at a step beyond ...