Early studies performed between 1946 and 1952 reported that cutaneously applied oestrogens had local effects in spite of probable systemic absorption. In order to test the validity of these observations the epidermal effects of topically applied 17β-oestradiol (E1) of 8 post-menopausal women were studied in a double-blind placebo-controlled cross-over study using non-invasive bioengineering techniques. E2 or placebo was applied twice daily for 45-50 days in a gel (at concentrations of 0.1 mg/g and 1.0 mg/g) and the results were compared. Changes in epidermal hydration (electrical capacitance and conductance) and mechanical properties were studied. We were unable to confirm the short-term local oestrogenic effects on post-menopausal human skin reported in the earlier studies. Thus, in spite of its high number of oestrogen receptors, the epidermis does not appear to be a target organ for oestrogens under clinical conditions.