Our objective was to determine the efficacy of megestrol acetate in the treatment of platinum-refractory epithelial ovarian cancer (EOC), and to evaluate the toxicities and quality of life (QOL) associated with this therapy. Patients with platinum-resistant epithelial ovarian cancer were treated with megestrol acetate (800 mg/day) orally for 28 days and then 400 mg/day for a minimum of 28 days before being assessed ready for evaluation of response to therapy. Patients who demonstrated a complete response (CR), partial response (PR) or stable disease were continued in the study until there was objective evidence of disease progression. All patients who went off study were followed up at regular intervals, every 2 months, to assess overall survival. Thirty-six patients were enrolled. Response was observed in seven of 36 patients (three CR and four PR). The response rate was 19.4% (95% CI 9-36). Four of the responders had the endometrioid cell type, while two were clear cell carcinoma and one was serouscystadenocarcinoma. All three CR patients had the histology of endometrioid carcinoma with the tumors located in the pelvis. Median survival of the study population was 5.8 months. Median survival in the responders was 12 months, while median survival in the non-responders was 5.5 months. Median progression-free survival in the responders was 8.3 months, while median progression-free survival in the non-responders was only 2 months. The majority of patients gained weight and had a fair quality of life score during treatment. The only toxicity observed was alopecia (grade 1) in four patients. We conclude that megestrol acetate has modest but definite activity in patients with platinum-refractory EOC, particularly in a small subset of the endometrioid subtype with limited disease in the pelvis. Only minimal toxicity was observed and the patients had a fair QOL score during the treatment.