During previous phase I experience of weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) used as a radiation sensitizer, decreased hematologic toxicity was noted. Therefore, an extended phase I/II trial of weekly paclitaxel in patients with chemotherapy-naive, metastatic non-small cell lung cancer was conducted to determine the maximum tolerated dose and activity of this alternative schedule. Twenty-six patients entered this study through six dose levels of paclitaxel (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered weekly for 6 of 8 weeks. Doses were escalated if more than 80% of the intended dose was administered in the preceding cohort without evidence of grade 3 nonhematologic toxicity. All patients had a performance status of 0 to 2 and a median age of 63 years. Sites of disease included the lung, bone, liver, soft tissue, and brain. Twenty-four patients completed the first 8-week cycle and are evaluable for toxicity and response. Dose-limiting toxicity occurred at 200 mg/m2/wk and consisted primarily of neutropenia. Only one evaluable patient required hospitalization for febrile neutropenia. Other toxicities included rash, pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine of 24 patients (38%) demonstrated objective responses. We conclude that the maximum tolerated dose of weekly paclitaxel administered for 6 weeks in an 8-week cycle is 175 mg/m2/wk. The response rate is encouraging and this schedule merits further investigation.