Tibolone (Org OD14) is a synthetic steroid with weak estrogenic, progestagenic and androgenic properties which is used for the treatment of menopausal complaints. Since the compound possesses estrogenic activity, it is important to assess its effects on pathways in breast cells involved in the development of breast cancer. In the present study we compared the dose-response effect (range: 5 x 10(-8) to 5 x 10(-5) M) of Tibolone and its metabolites (Org OM38, Org 4094, and Org 30,126) on the "sulphatase" pathway of two hormone-dependent human breast cancer cells: MCF-7 and T-47D; the results were compared with Norethisterone. After 24 hours incubation with physiological concentrations of estrone sulphate (E1 S: 5 x 10(-9) M) and high doses (5 x 10(-5) and 5 x 10(-6) M) of the different compounds, the conversion of E1 S to estradiol (E2) was strongly inhibited (85-98%) with all five substances tested. When low doses (5 x 10(-8) and 5 x 10(-7) M) were used, Tibolone and the metabolites Org 4094 and Org 30,126 were still very efficient at blocking the conversion of E1S to E2 (70-90%) in both cells. This inhibitory effect is less intense with the metabolite Org OM38 (45-70%). Norethisterone was the least potent antisulphatase agent (60-20%) tested. In conclusion, this very significant inhibitory effect of Tibolone and of its metabolites Org 4094 and Org 30,126 on the enzymes involved in the biosynthesis of E2 in human breast cancer cells, points to a potential beneficial effect of Tibolone which may be of relevance in its application for the treatment of climacteric complaints.