This study investigated the influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E2) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E2 was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3% +/- 9.5%, 70.0% +/- 5.1% and 57.3% +/- 5.3%, respectively (mean +/- SEM). Corresponding values for plasma E2 suppression were 30.7% +/- 6.5%, 43.4% +/- 4.5% and 42.9% +/- 6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E2 levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E2 suppression was observed. The suppression of E2 by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.