Objective: To test whether transdermal holmone therapy can be safely administered to postmenopausal women with chronic viral hepatitis B and/or C. Design: Eighty-one postmenopausal women with chronic viral hepatitis B and/or C and with severe vasomotor symptoms were treated for 5 years with transdermal estradiol (50 mu g/day) continuously and with transdennal norethisterone (250 mu g/day) for 14 days of every 28-day cycle. Another 95 women with viral chronic hepatitis but without climacteric symptoms were used as controls. Liver enzymes (glutamic-oxalacetic transaminase, glutamic-pyruvic transarninase, gamma-glutamine-transferase, and alkaline phosphatase) were measured every year. Results: At baseline, liver enzymes were similar in the two groups, with the exception of gamma-GT, which was slightly higher in untreated women (P < 0.01). Liver enzymes did not significantly vary with time in hormone-treated and untreated women. No significant difference was observed between the two groups. Conclusions: Transdermal estradiol and norethisterone can be safely administered for a prolonged period to postmenopausal women with chronic viral B and/or C hepatitis.