The sensitivity of normal tissues rather than of the tumour usually limits the effectiveness of cancer treatment. The normal tissue side effects from chemotherapy and/or radiotherapy result from both direct cellular loss and the extensive fibrosis that develops at the site of injury. Recent evidence suggests that the cytokine, transforming growth factor beta (TGF beta), mediates this fibrogenic process. Herein, we provide evidence in support of the hypothesis that the fibrosis formation following therapy results not only from TGF beta produced locally in the injured normal tissue, but also from circulating TGF beta released by the tumour. Thus, therapy-induced normal tissue damage appears in part to be a local manifestation of a systemic condition.