Forty-one patients with metastatic colorectal cancer were treated every four weeks with methotrexate 25 mg/m2 i.v. days 1, 8, 15; vincristine 1 mg/m2 i.v. day 1; lomustine 100 mg/m2 p.o. day 1. Inclusion criteria were: failure of previous 5-fluorouracil/leucovorin treatment; performance status (ECOG) 0-2; age less than 60 years; presence of symptoms; absence of concomitant diseases. Metastatic sites were: liver 30, lung 4, abdominal/pelvic mass 7. Three patients achieved partial responses (2 liver, 1 lung metastases); 4 showed stable disease and 34 progressed on therapy. The median survival of patients with partial response, stable disease and progression was comparable (24, 21, 22 weeks respectively). The most common toxicity was hematologic (thrombocytopenia and leukopenia). Other side effects included nausea and vomiting, stomatitis and diarrhea. Symptoms were not affected by treatment. We conclude that salvage chemotherapy is not recommended in colorectal cancer after 5-fluorouracil/leucovorin treatment even in patients with generally considered favorable characteristics for response to chemotherapy.