New agents active against unresectable metastatic and locoregional carcinoma of the esophagus or stomach are needed to improve patient outcomes. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be active against both adenocarcinoma and squamous cell carcinoma of the esophagus. A phase II study of paclitaxel 250 mg/m2 administered by 24-hour intravenous infusion every 21 days with granulocyte colony-stimulating factor (5 micrograms/kg/d subcutaneously 24 hours following paclitaxel) was conducted in such patients who had received no prior chemotherapy or biologic therapy. Of 33 patients with adenocarcinoma and 18 with squamous cell carcinoma, 16 (32%) had an objective response, including one complete response (CR); 11 others (22%) had minor responses. The CR, 11 of the partial responses (PRs), and six of the minor responses occurred among the 33 patients with adenocarcinoma. Granulocytopenia resulted in 11 hospitalizations in nine patients. Subsequently, paclitaxel (175 mg/m2 over 3 hours on day 1), cisplatin (20 mg/m2 days 1 through 5), and 5-fluorouracil (initially 1,000 mg/ m2, lowered to 750 mg/m2/d, by continuous infusion days 1 through 5) were administered every 28 days to patients with advanced adenocarcinoma (30) or squamous cell carcinoma (22) of the esophagus. Among 47 patients evaluable for response to date, four have had a CR and 17 a PR (overall response rate, 45%). Toxicity was moderate, and no treatment-related deaths occurred. Grade 3 or 4 nonhematologic toxicity was less frequent after the 5-fluorouracil dose was lowered. Response has been higher in squamous cell carcinoma patients. This combination should be explored further. In measurable metastatic gastric carcinoma, only one PR occurred among 20 previously untreated patients given paclitaxel 250 mg/m2 over 24 hours with granulocyte colony-stimulating factor in a phase II Eastern Cooperative Oncology Group study. Preliminary results from a phase II trial at the M.D. Anderson Cancer Center exploring the single-agent activity of paclitaxel 200 mg/m2 every 21 days without routine granulocyte colony-stimulating factor in previously untreated patients suggest definite, albeit low-level, activity against gastric carcinoma. Only one PR and three minor responses occurred among the first 15 patients who received paclitaxel in a 3-hour infusion. When the paclitaxel infusion was extended to 24 hours in this ongoing trial, three of the next 10 evaluable patients achieved a PR, with toxicity similar to that observed in other trials of paclitaxel at this dose range.