One hundred and ninety-seven patients with measurable metastatic cancer of the colon have been treated with one of four anticancer drugs which have had little prior trial in this disease. Objective tumor responses lasting a median of 9 weeks occurred with 0.5 g/m of streptozotocin given intravenously every week (10 percent), 130 mg/m of CCNU given orally every 6 weeks (10%), 1.0 mg/kg/day of 6-thioguanine given orally (8%), and 3 mg/kg/day of procarbazine given orally (3%). Performance status declined more rapidly with streptozotocin and 6-thioguanine and the median survival time was less (12 and 16 weeks respectively) than with procarbazine and CCNU (23 and 20 weeks respectively). This study suggests that procarbazine given in this way is ineffective but trials of streptozotocin or 6-thioguanine combined with other agents active against colon cancer should ensue as well as further exploration of the usefulness of other nitrosoureas.