We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal axis regulation in healthy women with no history of psychiatric illness by measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N = 23) and by measuring glucocorticoid receptor (type II) mRNA expression in lymphocytes using Northern blotting (N = 19). Both measures were performed in the early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone suppression of plasma cortisol was greater in the follicular phase of the menstrual cycle compared to the mid-luteal phase (p < .01). In addition, type II glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the follicular phase compared to the mid-luteal phase (p < .02). These results indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis is reduced in the mid-luteal phase of the menstrual cycle. Reduced feedback regulation of central stress response systems may play a role in generation of common premenstrual symptoms of irritability and dysphoria.