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Objectives: Our objectives were to confirm the activity of O-MAX chemotherapy in adenocarcinoma of the stomach and esophagus, particularly the high rate of complete remission (CR) and the relation of subclinical hemolysis to CR. Patients and Methods: Twenty-five patients with metastatic esophagogastric adenocarcinoma were treated with O-MAX. Two developed cancer-related hemolytic-uremic syndrome (C-HUS); both achieved CR. Subsequent patients were monitored for serum haptoglobin for subclinical hemolysis. Results: Median survival was 16.5 months. The objective response rate was 90%, with 38% CR. Three patients achieving CR relapsed in the central nervous system and died (2 without systemic disease). Four patients have remained alive, off therapy, the longest for 20 years. Two patients developed clinical C-HUS and 5 of 8 monitored patients developed subclinical hemolysis based on abnormal serum haptoglobin. Four of the patients with subclinical hemolysis achieved CR. Of the 7 patients developing clinical C-HUS or subclinical hemolysis, 6 (86%) achieved CR. Conclusions: O-MAX appears highly active in esophagogastric adenocarcinoma. A few long-term survivors of metastatic disease are being seen. CR and long-term survival appear to correlate with the development of hemolysis. Although highly promising, these results should be considered only as hypothesis-generating and require confirmation in a prospective trial.