A large number of drugs have been used to treat recurrent ovarian cancer, yet there are few data that guide the physician's choice. Typically, the decision to re-treat with platinum-based therapy depends on the progression-free interval. However, the optimum agent for the treatment of platinum-resistant or refractory disease is not defined. In this study, we investigated the efficacy of oral melphalan in patients who have platinum refractory or resistant disease. A retrospective analysis was performed on 22 patients with ovarian carcinomas who had relapsed within 6 months of their platinum-based chemotherapy and were treated with oral melphalan. No objective responses were seen and the median overall survival was 3 months from commencement of therapy. Although the treatment was generally well tolerated, only two of the 22 patients managed to complete the planned six cycles of treatment. At the time of analysis, only two patients were alive. Other nonplatinum compounds have demonstrated response rates in the region of 20% in similar patient populations and it is unlikely that any positive responses could have been missed by chance (95% CI 0-15.4). The results of this study serve to eliminate oral melphalan as a treatment option in patients with platinum-resistant or refractory ovarian carcinoma.