A highly sensitive radioimmunoassay was developed to measure the low serum concentrations of the endometrial secretory placenta protein 14 (PP14) in postmenopausal women. The assay was established by selecting optimum reaction conditions for radioactive labelling of PP14, combined with simple procedures for the purification of the labelled PP14. The PP14 assay was used in 2 groups of healthy, early postmenopausal women blindly receiving either estrogen monotherapy (n = 20, placebo n = 25) or continuously combined estrogen/progestogen therapy (n = 20, placebo n = 23). Neither of these regimens is believed to produce secretory endometrium. During the 12 months of estrogen monotherapy, serum PP14 (S-PP14) remained unchanged at 4.9 micrograms/l, when compared with placebo. Treatment with continuously combined estrogen/progestogen showed a small but significant increase in S-PP14 from 5.3 micrograms/l to 7.2 micrograms/l at 3 months. S-PP14 remained at this slightly elevated level throughout the treatment period of 24 months. Three months after hormone withdrawal, S-PP14 had returned to the pretreatment level. We suggest that S-PP14 might be a useful marker of secretory endometrium.