A B S T R A C T The decreasedl intestinal absorption of calcium and accelerated l)one loss associate(l with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to dlecreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean ±SE) in 13 patients duiring euglucocorticoidlisml-and dutring hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxyvitamin D concentrations (22+2-18±2 ng/ml; P < 0.05) lbut no significant chaniges in plasmiia 1,25-dihydroxyvitamini D (32 ± 8-23±+46 pg/ml) or serum immunoreactive parathyroi(l hormone (21±2-18±2 ,uleq/ml). Additionally, we studied plasmna kinetics of[3H] 1 ,25-dihydroxyvitamin D3 after intravenotus bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessmiient with a threecompartment model showe(d no significant abnormalities in production rates (hyperglucocorticoid patients 1.2±0.3 ,g/d, controls 1.5±0.2 ,ugld) or metabolic clearance rates (hyperglucocorticoid patients, 32 ± 3 ml/ min; controls 31+3 ml/min). Moreover, there were no significant differences in ciumulative excretion of radioactivity in urine (hyperglutcocorticoid patieints 18±2%; controls, 14±2%) or f'eces (hyperglucocorticoid patients, 60±9%, controls, 54+6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in hunIans. Thus, other mechanisms mutst be postulated to explain satisfactorily the abnormialities of bone structure and intestinal calciumn absorption that maiy occur after chronic glucocoi-ticoidl therapy.