The objective of this study was to optimize, in terms of endometrial receptivity (embryo implantation), the limits of unopposed administration of oestrogens beyond 35 days in an in-vitro fertilization (IVF) and ovum donation programme. Oocytes donated by 182 women undergoing IVF were distributed among 186 women treated by ovum donation. Five groups of recipients were established according to the duration of oestradiol valerate administration, in a 'prolonged follicular phase' protocol, before embryo replacement, employing oestradiol valerate at increasing doses up to 6 mg/day. Gonadotrophin-releasing hormone analogues (GnRHa) were simultaneously administered in ovulatory patients. The dosage of oestradiol valerate was maintained until oocytes were available for insemination and subsequent transfer. Donors and recipients were equally distributed among groups in terms of age and cause of infertility. There was no difference among groups in serum oestradiol concentration the day in which progesterone was added to obtain a secretory transformation of the endometrium. An analysis of the ovum donation cycles showed no difference among groups in pregnancy and implantation rates after the replacement of a similar number of embryos. Successful implantation was observed even after 100 days of unopposed oestradiol valerate administration. Break-through bleeding increasingly appeared according to the duration of oestrogen replacement. These clinical observations provide evidence that the concept of 'prolonged follicular phase' oestrogen replacement for ovum donation can be maintained, at least as long as 15 weeks. However, because of the high (> 44%) incidence of break-through bleeding after 9 weeks, it is advisable to stop oestrogen treatment at this point.(ABSTRACT TRUNCATED AT 250 WORDS)