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