Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess induced by environmental factors other than weightlessness that are associated with spaceflight experiments. To determine whether decreased osteocalcin, which may reflect altered bone formation rate, could be associated with corticosteroid excess, we measured serum osteocalcin in rats after injection of corticosterone or in response to various environmental stimuli. Exogenous steroid elicited a time- and dose-related decrease in serum osteocalcin, which was significant within 1 h of administration and maximally 25% below controls 1.5 h after injection of 3.3 mg corticosterone/kg body wt, the highest dose we tested. Adrenalectomy resulted in a 38% increase in osteocalcin. Exposure to environmental stressors lasting from 1.5 h to 3 wk also resulted in decreased osteocalcin levels, which showed a strong negative correlation (P less than 0.001) with serum corticosterone levels and adrenal mass after 1-3 wk of chronic cold exposure. Changes in serum osteocalcin were maximally about +/- 40% after 3 wk of chronic exposure to steroid excess or depletion. The response of osteocalcin to the well-defined adrenal hormone system implies an important role for corticosteroids in the control of serum osteocalcin.