Objective The purpose of this phase II trial was to evaluate the efficacy of intravenous paclitaxel in patients with recurrent or advanced leiomyosarcoma of the uterus. Methods To be eligible, patients with recurrent or persistent leiomyosarcoma of the uterus were to have measurable disease not previously treated with paclitaxel and adequate hematologic (WBC ≥3000/μl, platelet count ≥100,000/μl), renal (serum creatinine ≤2.0 mg%), and hepatic (bilirubin ≤ 1.5 × institutional normal) functions. Paclitaxel was given at a dose of 175 mg/m 2 (135 mg/m 2 for patients with prior radiotherapy) intravenously over 3 h every 3 weeks. Results Fifty-three patients were entered on this study; 48 were evaluable for toxicity and response. Fifteen had prior irradiation and 39 had prior chemotherapy. A median of 2 (range: 1–12) courses was given. Grade 4 neutropenia occurred in 3 (6.3%) patients. No grade 4 thrombocytopenia was reported and no deaths were attributable to therapy. Four (8.4%) patients had a complete or partial response and 22.9% had stable disease. Conclusions Although toxicity was minimal, this regimen demonstrated modest activity in patients with previously treated advanced or recurrent leiomyosarcoma of the uterus.