The aim of this study was to screen the inhibitory potential of different clinically used oestrogen and progestin hormones on CYP2C9, 2C19 and 3A4 activities in human liver microsomes. The degree of inhibition by desogestrel, 3-ketodesogestrel, 17-beta-oestradiol, gestodene, aethinyloestradiol, medroxyprogesterone acetate, norethisterone or L-norgestrel were studied at 100 microM on losartan oxidation (CYP2C9), R-omeprazole 5'-hydroxylation (CYP2C19) and R-omeprazole sulphoxidation (CYP3A4) with a 10-min preincubation with NADPH in human liver microsomes prepared from 6 individual genotyped donor livers. Aethinyloestradiol was found to be a potent inhibitor (55% mean inhibition; 95% CI 32% to 79%) of losartan oxidation (CYP2C9) and R-omeprazole 5-hydroxylation (70%; 63% to 77%) (CYP2C19), while it had little effect on R-omeprazole sulphoxidation (CYP3A4) activity. 17-beta-Oestradiol did not produce significant inhibition on any of the studied enzyme activities. Of the progestin hormones studied, gestodene and 3-ketodesogestrel were potent inhibitors of CYP2C19 (57%; 47% to 67% and 51%; 29% to 45%) and CYP3A4 (45%; 30% to 59% and 40%; 19% to 62%), but had little effect on the CYP2C9 activity. In addition, medroxyprogesterone acetate was found to inhibit CYP2C9 (55%; 45% to 65%), while not having significant effect on 2C19 or 3A4. In conclusion, the liability of clinically used female sex steroids to inhibit CYP2C9, 2C19 and 3A4 activities in human liver microsomes is very distinctive and these differences among both the oestrogen and progestin hormones may, at least in part, explain the variable results from clinical trials examining inhibitory effects of hormone replacement therapy and oral contraceptives on drug metabolism.