There is some evidence to suggest that transforming growth factor-β (TGF-β) mediates the cytostatic effects of the anti-oestrogen tamoxifen. In this study we have demonstrated that α-interferon has a significant anti-proliferative effect on the oestrogen receptor-positive human breast cancer cell line ZR-75. There is decreased phenotypic expression of the oestrogen receptors (to about 30% of control values) and increased TGF-β mRNA. Under the growth conditions used here, ZR-75 cells had approximately 5800 TGF-β binding sites per cell, with an apparent dissociation constant of 70 pm, and we have shown that the anti-proliferative effects of α-interferon can be reduced by 60% by co-treating the cells with a TGF-β polyclonal antibody. The cytostatic effects of α-interferon may therefore be mediated by TGF-β in this human breast cancer cell line.