Human epithelial ovarian carcinoma is well-known as a sex steroid-dependent neoplasm, but the possible biological significance of progesterone receptor (PR) in this cancer remains controversial. Recently, two isoforms of human PR, PRA and PRE, have been characterized and different functional characteristics have been reported for these two isoforms. We therefore examined immunohistochemistry (107 cases) and reverse transcription-polymerase chain reaction (RT-PGR) (16 cases) for PRA, PRE, and oestrogen receptor-a (ER-a). Labeling indices (LI) for PRA and PRE were 2.4 and 43.6, respectively, and the difference was statistically significant. PRE LI, but not PRA LI, as well as performance status, stage, and residual tumour turned out to be independent prognostic factors following multivariate analysis. There was also a significant correlation between ER-a LI and PRE LI (r = 0.595, P < 0.0001), suggestive of a possible interaction between these two receptors. RT-PGR also detected the expression of PR isoform transcripts in the same pattern as was observed with immunohistochemistry. Results of these studies indicate that PRA and PRE both mediate distinct pathways of progesterone action in ovarian carcinoma. Moreover, it is important to examine PRE tl as a prognostic factor in the cases of human epithelial ovarian carcinoma. (C) 2000 Cancer Research Campaign http://www.bjcancer.com.