Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.