Laboratory studies have suggested that rapidly alternating chemotherapy and radiation therapy might act synergistically. We undertook this study to evaluate the toxicity and effectiveness of this approach in patients with carcinoma involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47 patients (23 with carcinoma involving the hypopharynx arid 24 with carcinoma involving the esophagus) by three cycles of chemotherapy (during weeks 1, 4, and 7) rapidly alternating with twice-a-day radiution therapy (during weeks 2, 5, atid 8). Chemotherapy consisted of cisplatin 100 mg/m2and 5-fluorouracil 3–4 g/m2given over 4 days. Radiation therapy consisted of 180–200 cCy twice each day to 2000 ccylcycle, total 6000 cCy over 7 weeks. The histology was squamous cell carcinoma in 44 patients and adenocarcinoma in 3 patients with esophagus cancer. Median follow-up is 2 years (range 1–5 years). The observed survival rate for all 47 patients was 54% at 1 year and 38% at 2 years. Acute toxicity was considerable. Twelve patients (25%) died during therapy porn toxicity, without timor progression, leaving 35 patienrs (18 hypopharynx, 17 esophagus) evaluuble for response. Among the hypopharyngeal patients, 83% had a complete response, 11% had a partial response, and 6% had no response. Among the esophageal patients, 94% had a complete response, and 6% had a partial response. Local control was better for the esophageal patients than the hypopharyngeal patients (98% vs. 52% at 2 years, p = 0.038). The incidence of distant metastases was 25% at 2 years and not significantly different between the two groups. A high rate of local control was achieved, particularly in esophugeal cancer, by delivering chemotherapy and radiation therapy in a rapidly alternating fashion. This was achieved at a considerable cost in terms of toxicity, however. Although our response rates and local control compare favorably with those of other recently published studies of combined modality therapy in esophugus or head and neck cancer, much additional work is required to reduce the toxicity and, in hypopharyngeal cancer, to further improve the local control.