We studied the clinical and endocrine effects of the aromatase inhibitor formestane (4-hydroxyandrostenedione, 4-OHA) in heavily pretreated breast cancer patients (median number of previous endocrine treatments 2, range 1-4). Of 30 patients eligible for response evaluation, 3 patients (10%) showed a partial response while 11 patients (36.7%) experienced stable disease over a time period of at least 6 months. Plasma levels of oestrone, oestradiol and oestrone sulphate were found suppressed to a mean of 33.9, 35.6 and 24.2% of control values. 4 of 6 patients experienced a further substantial reduction in plasma oestrone sulphate to < 5% of pretreatment values when aminoglutethimide (AG) was added after relapse on 4-OHA monotherapy. Our findings suggest that these aromatase inhibitors may suppress plasma oestrogen levels by a percentage approaching the percentage inhibition of in vivo aromatisation measured by tracer techniques.