Forty post-menopause women using a preparation of 2 mg 17 beta-oestradiol and 1 mg norethisterone acetate (Kliofem) for a mean duration of 2.9 years were investigated in an open, prospective, method comparison study. Main outcome measures were the histology of endometrial biopsy in comparison with clinical evaluation of the endometrium during panoramic hysteroscopy and endometrial thickness measured by transvaginal ultrasound. Thirty-six women had either an inactive atrophic or unassessable endometrial biopsy, the remaining four (10%) showed benign endometrial changes. In the majority of patients the endometrium had a thin and regular appearance on hysteroscopy (92.5% of cases) with an endometrial thickness not exceeding 7 mm (90% of cases). Non-agreement between histology and hysteroscopy or transvaginal ultrasound findings was associated with the presence of polyps and submucosal fibroids, or innocuous endometrial changes such as a pseudodecidual pattern. No case of malignancy was encountered in any patient in this study. The present study suggests that continuous combined hormone replacement therapy appears to be safe with regard to endometrial health. In the majority of women an inactive endometrium or non-assessable biopsy result will be encountered. However, the numbers examined here are small and endometrial carcinoma has been reported to occur. Continuing follow-up of patients on continuous combined HRT is therefore essential.