One hundred and eight patients with residual epithelial ovarian cancer at second laparotomy, after first line plastine-based chemotherapy were treated with intraperitoneal rHU-interferon-gamma at a dose of 20 x 10(6) U/m2, twice a week for 3-4 months. 86% of the patients had residual macroscopic tumors and 33% bulky tumors (> 2 cm). From the 99 evaluable patients, 62 had an evaluative third laparotomy and nine additional patients a laparotomy. Complete pathologic and global response rates to interferon-gamma were 23 and 32% respectively. Age and tumor size were independently correlated with treatment response. Patients (n = 41) under the age of 60 with a tumor size less than 2 cm had a complete and global response rate of 42 and 54% respectively. Interferon-gamma was equally effective in chemo-resistant and chemosensitive tumors. Median duration of response was 21 months and median survival of responder patients was 86% at 2 years. In multivariate analysis, response to interferon-gamma was the most prominent prognostic factor of this population of patients with residual ovarian cancer.