The combined transdermal estradiol/norethisterone therapeutic system is designed to deliver both estradiol and norethisterone into the systemic circulation at a constant rate for up to 4 days when affixed to the skin. Transdermal administration avoids hepatic first-pass metabolism, allowing therapeutic concentrations of the progestogen and estrogen to be maintained in postmenopausal women following low dose administration. Transdermal norethisterone does not appear to alter the potentially beneficial effects of transdermal estradiol on total cholesterol, low-density lipoprotein (LDL) or triglyceride levels, or metabolic parameters of bone resorption or vaginal cytology. Protection of the endometrium from the effects of unopposed estradiol is achieved by sequential treatment with transdermal estradiol/norethisterone for 2 weeks of each 28-day cycle, and the majority of patients experience a regular vaginal bleeding pattern with this treatment regimen. Menopausal symptoms are improved to a similar extent during the transdermal estradiol-only and combined estradiol/norethisterone treatment phases. The transdermal therapeutic system has been well accepted by patients in clinical trials. It is generally well tolerated, the most common adverse effect being local irritation at the site of application. Estrogen- and progestogen-related systemic adverse events are reported in a small proportion of patients. Thus, the combined estradiol/norethisterone transdermal delivery system offers a more convenient and consistent method of progestogen administration. Together with its therapeutic efficacy when administered at lower dosages than oral therapy, it is likely to further improve patient compliance during hormone replacement therapy.