Interdisciplinary protocols for management of advanced adenocarcinoma of the ovary have resulted in prolonged patient survival. A subset of patients is emerging in whom central nervous system (CNS) relapse occurs even following negative second-look procedures (SLP). Seven of 342 eligible patients entered in a National Cancer Institute of Canada Trial for Ovarian Cancer, from February 1, 1980 to March 31, 1984, had CNS relapse. All patients received adriamycin and cisplatin. SLP was performed in 5 patients, 3 of whom were complete responders (CR). Two additional patients failed to complete their chemotherapy and had progressive pelvic disease. The median age of these 7 patients was 57 years, their overall survival time was 28 months, compared with an average age of 58 years and survival of 21.6 months, for the entire group. Two patients had prolonged survival after their CNS relapse; 1 patient lived 26 months, and the other, who underwent craniotomy for primary management of the metastasis survived 18 months. Confirmation of metastatic disease was obtained in 4 of the 7 patients. The results of this study suggest that management of CNS involvement in adenocarcinoma of the ovary should be determined by overall performance status even in the presence of generalized disease.