Prostate-specific antigen (PSA) is a serine protease with chymotripsine-like enzymatic activity, produced primarily by the prostate gland. It is widely used as a marker of androgen sensitive-prostate cancer. Likewise, women with androgen-dependent hirsutism have increased serum PSA levels. The aim of the present study was to investigate whether female patients with Cushing's disease had increased serum PSA concentrations. We studied 22 patients with active Cushing's disease. Twelve out of 22 patients were also evaluated after remission of the disease. Forty normal women with no signs of hirsutism served as controls. Mean serum PSA levels were higher in patients with active Cushing's disease than controls (p=0.005). Mean serum PSA levels decreased after remission of the disease (33.7+/-63.3 pg/ml vs 2.2+/-3.0 pg/ml, p<0.002, in active and cured patients, respectively). All patients with high serum PSA levels had a normalization of this parameter after the disease was cured. Serum T, DHEAS and delta4 concentrations decreased after the remission of Cushing's disease. A positive correlation was found between serum PSA and T values (r=0.6, p<0.05). In conclusion, elevated serum PSA values are markers of androgen activity in female with Cushing's disease and their normalization may represent an additional index of remission of the disease.