Prostate-specific antigen (PSA) is produced in several female tissues, under the regulation of steroid hormones. Serum PSA levels are increased in women with hirsutism, and they correlate with serum androgen levels. Therefore, as a marker of androgen excess, measurement of serum PSA may play a role in monitoring the treatment of hirsutism with contraceptive pills. Sixteen hirsute patients were included in the study. Clinical and biochemical variables, including serum PSA (using an ultrasensitive chemiluminescent immunoassay), total testosterone, sex hormone-binding globulin, androstenedione, dehydroepiandrosterone-sulfate, estradiol, and gonadotropin concentrations were recorded at baseline and after 3 and 6 cycles of treatment with a monophasic contraceptive pill containing ethynylestradiol and desogestrel. Twenty-seven healthy women served as controls for serum PSA level and for the serum androgen profile. Serum PSA levels were higher in hirsute patients, as compared with healthy women (mean +/- SEM: 0.014 +/- 0.003 vs. 0.006 +/- 0.001 microg/L, P < 0.02). Despite a marked decrease in serum androgens (total testosterone and androstenedione, calculated free testosterone and free androgen index; and dehydroepiandrosterone-sulfate) and in the hirsutism score, and a marked increase in sex hormone-binding globulin levels, serum PSA levels did not change and remained detectable in all the hirsute patients after 3 and 6 cycles of treatment with contraceptive pills. In conclusion, the increased serum PSA levels present in hirsute patients do not change during treatment with contraceptive pills and do not parallel the amelioration in hirsutism and the decrease in serum androgen concentrations that occur during this treatment. Thus, serum PSA measurements have no apparent role in the management of hirsute patients on oral contraceptive treatment, at least with the ultrasensitive assays currently available.