Lonidamine (150 mg x 3 day orally, days 1-5) plus high dose epidoxorubicin (120 mg/m2 intravenously, day 3) was tested in 26 patients with refractory or recurrent epithelial ovarian cancer, to assess the anti-tumour activity and the toxicity of this combination of drugs. All patients were evaluable for toxicity and 24 for tumour response. Two complete responses (8.3%) and six partial responses (25.0%) were recorded for a total response rate of 33.3%. 6 of 8 responding patients were pretreated with anthracyclines. Stable disease was obtained in 7 patients (29.2%). Toxicity was acceptable; only 1 (3.8%) patient stopped chemotherapy because of a left ventricular ejection rate reduction > 20%. The most relevant side-effect was leucopenia (grade 3-4, 34.6%). In conclusion, the association of lonidamine and high-dose epidoxorubicin has promising activity as second-line treatment in patients with refractory or recurrent epithelial ovarian cancer.