The effect of chronic glucocorticoid therapy on serum testosterone levels was studied in men aged 67 +/- 4 (SD) years with chronic pulmonary disease. The serum testosterone level was reduced in 14 of 16 patients to a mean value of 211 +/- 93 ng/dL, compared with 449 +/- 111 ng/dL in 11 age- and disease-matched control patients (p less than 0.001). The corticosteroid dosage and the serum testosterone level were inversely related (r = -0.78). Testosterone binding to serum proteins was not significantly affected. Basal gonadotrophin levels were not elevated while their secretory responses to exogenous gonadotrophin-releasing hormone (GnRH) were intact. We conclude that glucocorticoid therapy commonly reduces serum testosterone levels in older men due to alteration of hypothalamic GnRH secretion.