This phase II study was designed to analyze the efficacy and toxicity of an intravenous infusion of hydroxyurea in patients with ovarian cancer in which previous chemotherapy with platinum failed. Another phase II study of paclitaxel was run in the same patient population. Twenty-six patients with measurable ovarian cancer were entered in the hydroxyurea phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of a loading dose of 2,100 mg/m2 of hydroxyurea followed by a continuous intravenous infusion of 16,800 mg/m2 over 24 h repeated every 3 weeks. Patients with disease unresponsive to hydroxyurea could then be crossed over the paclitaxel. Disease in one patient responded, but the patient refused further treatment with hydroxyurea. Disease in 3 was stable. The median survival time was 8.8 months. The main toxic effect was neutropenia, with 31% of patients experiencing grade 3 or 4 neutropenia. No episodes of neutropenic fever were observed. Twenty seven percent of patients presented with anemia and thrombocytopenia. Other side effects were all lower than grade 2 and included gastrointestinal dysfunction (35% of patients), alopecia (12%), dermatitis (12%), headache (8%), and stomatitis (4%). We conclude that high-dose hydroxyurea administered parenterally as a single agent over 24 h is not active in patients with platinum-refractory ovarian cancer but is subjectively well tolerated.