36 previously treated patients (25 with anthracyclines) with advanced epithelial ovarian cancer have been treated with intraperitoneal (i.p.) mitoxantrone (M) at increasing doses. The response was evaluated through repeated laparoscopy with multiple biopsies and serial measurement of Ovarian Cancer Antigen 125 (CA 125); 11/36 patients had a complete (6 patients) or partial (5 patients) response. Toxicity (both local and general) was observed starting from 25 mg/m2 of M per cycle. The amount of drug reaching systemic circulation was monitored by measuring M plasma value after i.p. treatment. This study showed wide variations in serum levels obtained after i.p. doses ranging from 23 to 36 mg/m2. The area under the curve (AUC) of mitoxantrone plasma samples, did not correlate with the i.p. administered dose. Conversely, a correlation seems to exist between the plasma AUC and the responder status. Patients who showed clinical responses to i.p. treatment with mitoxantrone had AUCs and plasma peak levels of the drug that were significantly higher than those in non-responders (P = 0.03, Fisher's exact test).