Advanced metastatic non-small cell lung cancer (NSCLC) that has progressed on initial cisplatin-based chemotherapy has a poor prognosis. Although paclitaxel is an active agent in the first-line therapy of NSCLC, 24-hr infusion of paclitaxel in patients with NSCLC failing first-line cisplatin-based regimens has shown minimal activity. Prolonged infusions of paclitaxel have shown activity in breast cancer patients who have failed short infusions of paclitaxel. In this study, 13 patients with refractory NSCLC who progressed on or after initial chemotherapy were treated with 96-hr paclitaxel (140 mg/m2 over 96 hr every 3 weeks) infusions as outpatients using a CADD infusion pump via a central catheter. Nine patients received only one or two cycles of treatment because of disease progression and had a median survival of 3 months (range, 1-5 months). Four patients had stabilization of disease for two to six cycles of treatment and had a median survival of 8 months (range, 8-12+ months). Grade 3-4 hematologic and nonhematologic toxicity occurred in < 10% of cycles, and no treatment-related hospitalizations occurred. Quality of life (QOL) assessments using the Functional Assessment of Cancer Therapy-Lung questionnaire were performed at baseline and with each treatment cycle. In conclusion, although no objective responses were seen, disease stabilization occurred in 31% of patients. Overall toxicity was tolerable with no major negative impact on QOL in those patients receiving two or more cycles of treatment.