This study examined the fine structure of the human endometrial glandular epithelium after the administration of a single dose of RU486 (mifepristone), given in the early luteal phase. The drug was administered on days 2, 3, 5 and 6 after the luteinizing hormone peak (LH + 0). Biopsies were performed on days LH + 5, 6, 8 and 9. These were compared with control biopsies taken on corresponding days. Qualitatively, the main cytological effect of the RU486 was on the secretory apparatus and on the polarity of the cell. The formation of the nuclear channel system was also affected by the drug. A two-way analysis of variance on cell and nuclear volume data revealed no significant effect of day of biopsy, condition or interaction. Mitochondrial volume and secretory apparatus volume data revealed a significant effect of day of biopsy and interaction term; mitochondrial volume at LH + 5 was 95.9 +/- 25.3 microm3 (mean +/- SD) for control and 57.7 +/- 31.9 microm3 for RU486-treated epithelium. The volume of the secretory apparatus in the treated group was smaller on days LH + 5 and 6 (14.6 +/- 4.2 microm3, 6.41 +/- microm3) when compared to day-matched control biopsies (35.9 +/- 10.5 microm3, 41.7 +/- 26.4 microm3). RU486 administration in the early luteal phase disrupted the secretory activity of the cells. These findings provide an insight into the cellular mechanisms of progesterone receptor blockade in the peri-implantation period.