The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation therapy (RT) for previously untreated, locally advanced non-small cell lung cancers. Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell cancer ineligible for potentially curative surgical resection, a good performance status, adequate hematologic, hepatic, and renal functions, and no distant metastases. All patients receive a total tumor dose of 64.8 Gy megavoltage RT in 7 weeks at 1.8 Gy once daily, 5 d/wk. Paclitaxel is delivered by continuous intravenous infusion starting 48 hours before RT and continuing for its duration. The dose of paclitaxel is escalated in cohorts of three patients in a standard phase I design. To date, 16 patients have entered the trial, and 15 are evaluable for toxicity in this ongoing study. Paclitaxel dose is currently at a 6.5 mg/m2/d dose level, with no dose-limiting toxicity recorded thus far. One patient at the highest dose level has had grade 2 pneumonitis. With the exception of anemia, toxicities are those that would be expected from RT alone. A slowly progressive normocytic anemia with no renal dysfunction was found to be associated with an acquired hypoerythropoietin state. These findings indicate that this therapy is feasible and well tolerated through current dose levels, with no dose-limiting toxicity. Dose escalation is ongoing.