To investigate the role of cortisol in the etiology of insulin resistance in men and women, we examined 218 healthy non-hospitalized elderly, selected from the Rotterdam Study. Free cortisol was assessed by the ratio of fasting serum cortisol over corticosteroid-binding globulin (CBG), and insulin resistance was estimated by the fasting insulin level. CBG was higher in women and decreased with age. In both men and women, the early morning free cortisol level showed no association with age or waist/hip ratio. In men, an inverse association between cortisol and body mass index was observed. In women, higher cortisol levels were associated with increased insulin levels; an increase of 9.7 mU/l insulin per unit cortisol/CBG (S.E. 3.9, P = 0.01). The association did not change after adjustment for age, body mass index or waist/hip ratio. The results of this study in elderly subjects suggest that in women cortisol may be implicated in the age-associated insulin resistance.