To evaluate any beneficial effect of progesterone supplementation during the luteal phase of GIFT or IVF cycles stimulated by clomiphene citrate and HMG, two random prospective studies were performed. In the first study, a group of patients received a luteal phase supplement of 50 mg natural progesterone i.m. daily from the day of oocyte retrieval onwards. Initial results on 168 patients indicated that the pregnancy rate was similar in patients with or without progesterone supplements. No differences were found between the two groups in an analysis of pregnant and failed cycles. In a second study two different protocols of luteal phase supplementation after Buserelin-HMG stimulation were compared: natural progesterone in combination with oestradiol valerate (50 patients) or HCG supplements (41 patients). A 32% pregnancy rate per cycle was encountered in both groups. Endometrial biopsies, taken during the luteal phase from patients who did not undergo embryo replacement, revealed retarded endometrial development in most of the biopsies.