Between 1980 and 1988, 91 patients with adenocarcinoma of the esophagus were treated by surgical resection and selective postoperative therapy. Operative mortality was 2%. Pathologic stage was I in 4, II in 26, and III in 61. Actuarial 2- and 5-year survival was 24% and 8%. From 1987 to 1989, 16 patients with adenocarcinoma of the esophagus were treated with two cycles of 5-fluorouracil and cisplatin followed by surgical resection. There was 1 complete response (6%), 5 partial responses (31%), and 10 with no response (63%). Twelve patients had resection. Pathologic stage was I in 1, II in 4, and III in 8. There was one chemotherapy-related death and one surgical death. Actuarial 4-year survival is 42%. From 1990 to 1993, 22 patients with adenocarcinoma of the esophagus were treated with two cycles of etoposide, doxorubicin, and cisplatin followed by surgical resection. There was 1 complete response (5%), 11 partial responses (50%), and 10 with no response (45%). Eighteen patients had resection. Pathologic stage was 0 in 1, II in 8, and III in 9. There were no treatment-related deaths. The actuarial 2-year survival is 58%. Conclusions are necessarily limited because the patients were not treated in a randomized fashion. These preliminary results with preoperative chemotherapy appear improved (p = 0.04 and p = 0.004, respectively) as compared with results from 1980 to 1988 without preoperative chemotherapy.