The objective of this study was to examine the results of two hormonal treatment modalities on subjects who had persistently abnormal endometrial development in the luteal phase. A prospective study design was used to investigate 14 women who had persistently retarded endometrium associated with infertility (n = 11) or recurrent miscarriage (n = 3). Treatment A consisted of progesterone supplementation in the form of i.m. progesterone at a daily dose of 25-50 mg starting on day luteinizing hormone (LH) + 1 for 14 days. Treatment B consisted of artificial cycles produced after down-regulation of the hypothalamic-pituitary-ovarian axis with Goserelin (3.6 mg s.c.) followed by the administration of a standard hormone replacement therapy. Endometrial biopsy was taken on day 19 of the artificial cycle or days LH + 5 to +7 in the progesterone supplementation cycle. A histological study was made of the endometrial specimens by standard dating criteria and morphometry. The artificial cycle resulted in normal development in all subjects (n = 11), whereas progesterone supplementation restored normal endometrial development in only seven of 11 (64%) subjects. We conclude that persistently retarded endometrium could be treated more effectively with the artificial cycle than with progesterone supplementation.