Twelve ovarian cancer patients who failed chemotherapy entered a Phase I trial of intraperitoneal 177Lu-CC49 antibody. Methods: Patients had disease confined to the abdominal cavity ± retroperitoneal lymph nodes, adequate organ function and no previous radiation. Results: Side effects included mild discomfort with administration (1/12), delayed transient arthralgia (2/12), and mild marrow suppression (calculated marrow doses of 11-54 cGy). The maximum tolerated dose has not been reached with levels of 10, 18, 25 and 30 mCi/m2. Radioimmunoscintigraphy revealed localization consistent with tumor in 11 of 12 patients. One of eight patients with gross disease had >50% tumor reduction after therapy, while six progressed and one went off study with stable disease. Of patients with microscopic or occult disease, one relapsed at 10 mo and three remain without evidence of disease after 18 mo. Conclusion: Intraperitoneal radioimmunotherapy with 177Lu- CC49 is well tolerated and appears to have antitumor activity against chemotherapy-resistant ovarian cancer in the peritoneal cavity.