A phase I study was undertaken in order to establish the maximum tolerated dose of intra-hepatic arterial 5-fluorouracil (5-FU) when given in combination with systemic folinic acid. Patients with colorectal liver metastases (n = 10) received escalating doses of 5-FU as a 24 h infusion with a fixed dose (400 mg m-2) of intravenous folinic acid once per week. Dose limiting toxicity (WHO grade greater than 2) was encountered at 2 g m-2 5-FU. Principal adverse effects were diarrhoea, vomiting and oral ulceration. The recommended dose for phase II studies is 1.5 g m-2 week-1 24 h 5-FU regional infusion with 400 mg m-2 week-1 intravenous folinic acid.