It is commonly thought that patients receiving exogenous glucocorticoids have suppression of the hypothalamic-pituitary-adrenal axis and need high supplemental doses of exogenous glucocorticoids (so-called stress steroids) to meet the demands of operative stress. Several reports have suggested that clinically important suppression of the hypothalamic-pituitary-adrenal axis is extremely uncommon and that the levels of glucocorticoids required for stress are much lower than previously believed. A prospective study of twenty-eight patients who had thirty-five major orthopaedic operations was conducted. No patient received stress steroids; they were given only the baseline immunosuppressive doses of glucocorticoids (mean dose, ten milligrams of prednisone). Clinical information (based on regular physical examinations for signs and symptoms of hypotension, myalgia, arthralgia, ileus, and fever) and laboratory data (serum sodium levels, eosinophil count, and twenty-four-hour urinary free-cortisol levels, determined at perioperative and non-stress postoperative time-periods) were obtained to document any evidence of adrenocortical insufficiency. There was no such evidence in any of the patients, who were monitored during their entire hospitalization. The levels of twenty-four-hour urinary free cortisol showed that all patients had endogenous adrenocortical function and, when this information was considered together with the clinical outcome, it was concluded that this level of function was sufficient to meet the demands of operative stress. Adrenocortical insufficiency in patients who have orthopaedic operations without receiving supplemental stress steroids appears to be much less common than previously thought. While biochemical testing of the function of the hypothalamic-pituitary-adrenal axis may sometimes reveal evidence of adrenal insufficiency, these tests do not predict the clinical outcome and may be too sensitive to guide decisions regarding treatment. Supplemental exogenous stress glucocorticoids may not be needed to meet the demands of operative stress in these patients.