Purpose: We wished to critically examine the level of activity of weekly paclitaxel in a patient population with well -characterized platinum/paclitaxel-resistant (3-week schedule) ovarian cancer. Patients and Methods: Eligibility criteria for this phase II trial included the following: ovarian and fallopian tube cancers or primary carcinoma of the peritoneum; prior initial therapy with platinum/paclitaxel; and failure to respond to treatment (progression or stable disease as best response), or a response duration of less than 3 months, or if the response was more than 3 months, retreatment with both agents required and failure to respond a second time or the response duration was less than 3 months. Measurable or assessable disease (CA-125 response criteria) was required. Patients received weekly paclitaxel (80 mg/m2) until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. Results: Fifty-three patients (52 assessable for toxicity and 51 for response) were entered onto this multiinstitution trial. Of 248 total cycles (887 doses), only 13 (1%) were modified (dose reduction or treatment delay) because of side effects. Therapy was discontinued in five patients because of toxicity (four because of peripheral neuropathy, and one because of painful fingernail beds). Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an objective response (four by CA-125 criteria, and nine by ≥ 50% reduction of measurable disease). Conclusion: Weekly paclitaxel (80 mg/m2) is generally well tolerated and is an active second-line regimen against ovarian cancer that has demonstrated resistance to platinum/paclitaxel delivered on an every-3-week schedule.