Serum osteocalcin (OC) levels were measured in 19 asthmatic patients receiving long term glucocorticoid therapy and in age- and sex-matched asthmatic patients not receiving this treatment. In the glucocorticoid-treated patients, the mean OC level was approximately 50% less than that in the control group (P less than 0.001), and there was a direct correlation between serum OC and 1,25-dihydroxyvitamin D [1,25-(OH)2D; r = 0.71; P less than 0.001]. Multiple regression analysis in a total of 39 glucocorticoid-treated patients indicated that OC correlated directly to 1,25-(OH)2D and inversely to glucocorticoid dose. There was no correlation between OC and 1,25-(OH)2D in the control group and no significant difference in mean serum 1,25-(OH)2D between the steroid-treated asthmatic patients and the asthmatic control patients. The effect of a 4-day course of oral 1,25-(OH)2D on serum OC was studied in six patients with glucocorticoid excess and six normal subjects. There was a similar percent increase in OC levels in both groups, though the basal concentrations and absolute increases were substantially less in the steroid-treated group. It is likely that the depression of serum OC in glucocorticoid-treated patients results from the reduction in the rate of bone formation induced by these hormones.