Twelve hundred ninety-six patients with resected colon cancer that was either locally invasive (stage B2) or had regional nodal involvement (stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. We also randomly assigned patients with stage C disease to treatment with levamisole alone. At the time of this writing, the median follow-up time is 3 years (2 to 5.5). Among the stage C patients, treatment with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41% (P < 0.0001). The overall mortality rate was reduced by 33% (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the stage B2 patients were inconclusive and preliminary. The adverse effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia. Levamisole plus fluorouracil cause essentially the same adverse effects as those of fluorouracil alone, specifically, nausea, vomiting, stomatitis, diarrhoea, dermatitis, and leukopenia. Usually, these reactions were not severe and did not greatly impede patients’ compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for stage C colon carcinoma. Since community oncologists treated most of the patients in our study, this approach is readily adaptable to standard medical practice.