Matrix metalloproteinases (MMPs) are implicated in tumour invasion and metastasis. We report the first use of an MMP inhibitor to treat unresectable cholangiocarcinoma. Four men with stage IV cholangiocarcinoma received oral Marimastat (10 mg bd) indefinitely following relief of obstructive jaundice. Monthly measurements of the tumour marker CA 19-9 were used as an indicator of disease response and activity. CA 19-9 levels dropped sharply and stayed low in the two patients who appeared to respond. Mean survival of the four patients was 21.5 months (range 4-48 months). Side effects were well tolerated. A more extensive and detailed examination of MMP inhibitors to treat cholangiocarcinoma is indicated.