4-Hydroxyandrostenedione (4-OHA) is a specific inhibitor of aromatase activity used for the treatment of breast cancer in post-menopausal women. Treatment with 4-OHA has been shown to inhibit the peripheral conversion of androstenedione to oestrone and reduce plasma oestrogen concentrations, but the effect of treatment on breast-tissue oestrone concentrations is not known. We have therefore examined the effect of treatment with 4-OHA on oestrone concentrations in normal and malignant breast tissues and also measured plasma and tissue 4-OHA concentrations. Changes in tumour oestrone concentrations were related to DNA polymerase alpha activity, a marker of cellular proliferation. Blood and breast-tissue samples were obtained before and 36 hr after treatment with 4-OHA. The mean plasma concentration of 4-OHA was 27.9 +/- 19.3 ng/ml, compared with levels of 33.7 +/- 25.6 ng/g for breast tumour and 13.5 +/- 11.5 ng/g for normal breast tissue. There was a significant correlation between 4-OHA concentrations in plasma and normal breast tissue (r = 0.91, p less than 0.001). Treatment with 4-OHA resulted in a significant (p less than 0.02) decrease in breast-tissue oestrone concentrations. For 3/4 tumour samples, a marked decrease in the concentration of oestrone (78 +/- 4%) was associated with a similar decrease (64 +/- 16%) in DNA polymerase alpha activity. It is concluded that treatment with 4-OHA effectively reduces breast-tissue exposure to oestrogen.