We hypothesized that the activity of the hypothalamus-pituitary-adrenal system in depressed patients is related to oral glucose tolerance. In 70 moderately depressed inpatients, we measured morning saliva cortisol for 6 days and assessed oral glucose tolerance. We found glucose concentrations to be positively associated with mean morning cortisol concentrations (F3,236 = 2.86, p < 0.05). Also, the ISI, a measure of insulin receptor sensitivity, was negatively associated with mean morning cortisol concentrations (r = -0.25, p < 0.04). These findings support the hypothesis that hypercortisolemia may lead to disturbed glucose utilization in depressed patients.