Young healthy men were studied during brief treatment with prednisone to determine the rapidity of the effects of glucocorticoids on serum osteocalcin. Seven subjects were given 60 mg of prednisone orally at 8 a.m. on 5 consecutive days. Serum osteocalcin fell to 68% of the pretreatment level within 24 hours after the first dose was administered (p less than 0.01) and reached a nadir of 37% of baseline between 48 and 96 hours after treatment was begun (p less than 0.005). When prednisone was discontinued, serum osteocalcin returned promptly to pretreatment levels. Similar, though less marked, effects were found with lower doses of prednisone. Serum osteocalcin was not different from baseline after 5 mg of prednisone in five subjects, but after treatment of five subjects each with 10, 15, or 20 mg of prednisone, osteocalcin levels were 83%, 78%, and 74% of baseline, respectively (p less than 0.05). Serum osteocalcin levels fell rapidly with glucocorticoid administration, indicating that the effects of glucocorticoids on bone cells may be demonstrated long before clinical evidence of osteoporosis becomes apparent.