As an extension to a previous study to examine the effects of clomiphene citrate (CC) on human chorionic gonadotrophin/luteinizing hormone (LH) receptors in human corpora lutea, we sought to determine the effect of CC on the synthesis of the beta-lactoglobulin homologue, pregnancy associated endometrial alpha 2-globulin (alpha 2-PEG) by the luteal phase human endometrium. Seventeen normally-cycling women aged 25.9 +/- 2.1 years (mean +/- SE), undergoing elective tubal ligation, were divided into four groups consisting of controls (n = 2) and three treatment groups. Each of the treatment groups (n = 5/group) was treated with either 50 mg (group 1), 100 mg (group 2) or 150 mg (group 3) of CC daily on days 5 to 9 of the cycle. Portions of endometrial tissue were obtained by curettage 7 to 9 days following the urinary LH surge and were either fixed for histological analyses or cultured in vitro in the presence of [35S]methionine. Tissue media (TCM) that were analysed by two-dimensional gel electrophoresis followed by fluorography indicated that the synthesis of alpha 2-PEG was most markedly reduced in groups 2 and 3. Densitometric scans of TCM Western blots and radioimmunoassay (RIA) of TCM showed that the overall synthesis of alpha 2-PEG decreased from 5.8 +/- 1.9 arbitrary units (AU) and 371.2 +/- 239.3 ng/ml in group 1 to 3.1 +/- 0.8 AU and 69.4 +/- 24.9 ng/ml, and 2.7 +/- 1.1 AU and 52.4 +/- 19.8 ng/ml in groups 2 and 3 respectively. On cycle days 20-22, control values were 5.8 AU and 498.1 ng/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS)