Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been studied primarily on a 3-week schedule as a 3-, 24-, or 96-hour infusion at doses ranging from 135 to 250 mg/m2. The observed toxicity profile seems to be both dose and schedule dependent. Dose densification of paclitaxel given weekly over 6 weeks on a split-dose schedule for an overall increase in dose intensity was thought to improve the therapeutic index of paclitaxel in a variety of advanced malignancies and to be suitable for outpatient administration. For this study, chemotherapy consisted of a weekly 1-hour infusion of paclitaxel at a starting dose of 40 mg/m2/wk for 6 weeks, followed by a 2- to 3-week interval. Paclitaxel dosage was escalated in 10 mg/m2/wk increments in subsequent patients, to a maximum dosage of 90 mg/m2/wk. Intravenous dexamethasone, cimetidine, clemastine, and ondansetron were administered immediately before the paclitaxel infusion. Fifty patients participated in the study. The male to female ratio was 21 to 29, the median age was 53.2 years (age range, 33 to 74), and the median performance status was 1. All patients were chemotherapeutically pretreated. Overall response included five complete responses (10%), 15 partial responses (30%), 19 no change (38%), and 11 disease progressions (22%). Median dose intensity was 410 mg/m2/6 wk (range, 200 to 540 mg/m2/6 wk). Hematologic toxicity was mild, with no grade 3 or 4 toxicity up to 90 mg/m2/wk. No hypersensitivity reactions or neurologic or cardiac toxicities were documented. Dose-densified, weekly paclitaxel is concluded to be active in a variety of pretreated tumor entities. The overall low hematologic and peripheral toxicity profile suggests that further dose intensification of weekly paclitaxel and/or combination with other cytotoxic agents (eg, cisplatin/carboplatin, ifosfamide, etoposide) may be warranted. Paclitaxel can be given safely in the outpatient setting. Paclitaxel 90 mg/m2/wk is recommended for single-agent treatment. Dose-densified paclitaxel may be considered a valuable and promising alternative to standard 3-week treatment, with further options possible in combination chemotherapy.