To explore the potential therapeutic differences between 3- and 96-hour infusions of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory malignant diseases, we conducted a phase II study in which patients were treated first with paclitaxel 135 mg/m2 by 3-hour infusion. If patients did not respond or relapsed after response, they were then treated by 96-hour infusion of paclitaxel at the same dose. Patients with metastatic or incurable breast, ovarian, lung, head/neck carcinomas, and lymphoma were eligible. They were required to have an Eastern Cooperative Oncology Group performance status of 2 or better and adequate hematologic, hepatic, and renal functions. In 22 patients entered thus far, we have observed one partial response in 10 lung cancer patients treated by 3-hour paclitaxel and one partial response in six patients treated by 96-hour infusion. Four partial responses were observed with 3-hour paclitaxel alone in nine breast cancer patients, while three partial responses occurred in five patients with 96-hour infusion after the 3-hour infusion failed. Nonhematologic toxicities such as fatigue, peripheral neuropathy, and mucositis occurred more commonly in the 96-hour infusion group. Our preliminary results suggest (1) that 3-hour infusion of paclitaxel is active against refractory breast cancer, (2) that 96-hour infusion of paclitaxel can induce partial response in breast cancer that was refractory to 3-hour treatment of paclitaxel, and (3) that more studies are needed to define the optimal treatment schedule of paclitaxel.