A phase II trial was designed to determine whether mistletoe extract can induce objective tumor response in patients with metastatic colorectal cancer resistant to 5-fluorouracil and leucovorin (5FU/LCV)-based chemotherapy. Twenty-five patients (15 female, 10 male; median age 69 yr) were treated with commercially available mistletoe extract (Abnoba-viscum Quercus) given by three weekly subcutaneous injections with daily dose gradually increased from 0.15 to 15 mg plant extract. Treatment was discontinued if unacceptable toxicity developed or if the patient became bedridden. Median duration of treatment was 14 wk (range, 4-66 wk). Treatment was continued in 14 patients until they became bedridden, and 11 patients decided to discontinue the treatment after their illness progressed. Objective tumor response was not seen in any of the 25 patients (0%, 95% confidence interval 0-13.7%). Stable disease, lasting for a median of 2.5 mo (range, 1.5-7 mo), was noted in 21 (84%) patients. Median survival was 5.5 mo and symptomatic relief was reported by 10 (40%) patients. Toxicity was mild and included mainly local inflammatory reaction. In conclusion, mistletoe extract does not seem to be active in metastatic colorectal cancer resistant to 5FU/LCV in terms of objective tumor response.