It is well established that estrogens and progestogens are able to influence the vasotonus in postmenopausal women. The present study was undertaken to find out if the NO/cGMP-system is involved in this hormone action. Urinary cGMP excretion which can reflect intracellular cGMP production elicited by NO (EDRF) was investigated in 20 postmenopausal women. In an open cross-over study design norethisterone acetate was administered orally for 8 days, estradiol valerate orally for 9 days and a combination of both substances for 12 days. After all three treatment phases urinary cGMP expressed as percentage of the pretreatment value was increased at a statistically significant level. Due to high individual variations no significant differences could be found among the values after the three treatment phases. It was concluded that the NO/cGMP-system may play a role in maintaining vasotonus in postmenopausal women under hormone replacement therapy.