To establish the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a radiosensitizing agent and to determine its optimal therapeutic dose when combined with conventionally fractionated radiotherapy in the treatment of non-small cell lung cancer, a phase I/II study was undertaken in 16 treatment-naive patients. Beginning at 40 mg/m2/wk with doses escalated in 10 mg/m2 increments until dose-limiting toxicity was encountered, paclitaxel was administered over 3 hours to successive three-patient cohorts. Radiotherapy (2 Gy/d x 5 d/wk; maximum total dose, 50 Gy) was delivered after the paclitaxel infusion. Treatment continued for 5 successive weeks. All 16 patients are evaluable for response and toxicity. Hematologic toxicity was low, with red blood cells and platelets remaining stable and leukocyte decreases (mean, 60%) attributed to radiotherapy. Nonhematologic toxicity included grade 2/3 esophagitis and neurologic sequelae. Responses were noted at all paclitaxel dose levels, including two complete and five partial responses, but the median time to progression was only 5 months. Paclitaxel may be combined safely with radiotherapy without major toxicity, and the radiosensitizing effect of paclitaxel was evident at all doses.