Objective. Intraperitoneal interferon-α (IP-IFNα) has shown some benefit in the treatment of patients with ovarian cancer. Our goal was to evaluate the use of low-dose IP-IFNα for the palliative control of ascites in non-ovarian gynecologic malignancies, including primary peritoneal and uterine papillary serous carcinomas. Methods. Fifteen patients with non-ovarian gynecologic malignancies received one or two doses of 10 MU (10 × 106 U/m2) of IP-IFNα via single-use drum catheter for the symptomatic control of ascites. The median age for this patient group was 61 years (range 40-84). Histopathologic diagnoses were confirmed on all patients. Eleven of 15 (73%) patients had uterine cancers. Four of 15 (27%) patients had papillary serous primary peritoneal carcinomas. Thirteen of 15 (87%) patients had Stage III disease or more. All patients had been heavily pretreated with chemotherapy and all had progressive disease. Results. Specific parameters used to evaluate IP-IFNα were (1) median survival; (2) number of days to recurrent ascites; (3) number of subsequent paracenteses required for symptomatic relief; and (4) symptomatology and side effects. Median overall survival was 3 months (range 0.5-13). Seven of 15 (47%) patients survived >3 months. Twelve of 15 (80%) patients had recurrent ascites within 30 days of treatment. However, 3/15 (20%) patients had a prolonged, >30-day period, without symptomatic ascites. One patient (6%) had a 270-day response with no ascites. Toxicity was minimal from IP-IFNα infusion. The most common side effect was fever in 6/15 (40%) patients. Conclusion. IP-IFNα was well tolerated and may have some benefit in a subset of patients. Although 80% of patients had recurrent ascites within 30 days, 20% had a prolonged, >30-day response. Further study is warranted to determine the role of immune modulators, such as IP-IFNα, in the palliative management of patients with non-ovarian gynecologic malignancies that cause ascites.