A phase I study was conducted to investigate the safety and efficacy of twice-weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and concurrent thoracic irradiation in patients with stage III non-small cell lung cancer. Radiation therapy beginning on day 1 was delivered in 1.8- to 2.0-Gy daily fractions, to a total dose of 61 Gy. Paclitaxel at a starting dose of 25 mg/m2/d was administered intravenously over 1 hour before daily radiation on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39, for a total of 12 doses over 6 weeks. The paclitaxel dose was escalated by 5 mg/m2/d in each cohort of patients to determine the maximum tolerated dose. The highest paclitaxel dose reached was 40 mg/m2/d, as defined by dose-limiting toxicities of esophagitis and desquamation within the radiation fields. For each dose group, the median total number of paclitaxel doses administered was 12 and the median total radiation dose was 61 Gy. Response rates ranging from 50% to 100% were observed (three of six patients at paclitaxel 25 mg/m2, four of six at 30 mg/m2, seven of seven at 35 mg/m2, six of six at 40 mg/m2), for an overall response rate of 80%. We conclude that the maximum tolerated dose of paclitaxel is 35 mg/m2 given twice weekly in a 1-hour infusion for 6 weeks concurrently with thoracic irradiation. This study provides the basis for an ongoing trial combining twice-weekly paclitaxel and carboplatin with concurrent thoracic irradiation for patients with stage III non-small cell lung cancer.