The effectiveness of melphalan, hexamethylmelamine, and 5-fluorouracil was compared in the treatment of patients with advanced ovarian cancer. Patients responded the best to hexamethylmelamine, which, however, was associated with considerable neurotoxicity. Patients responded the worst to 5-fluorouracil, which occasionally induced severe gastrointestinal toxicity. Patients treated with melphalan continued to demonstrate the response rate reported for several years in the literature. Melphalan seemed the best choice as a second-line drug. It induced not only the longest survival rate among patients, but also the only two complete responses as a second-line drug. Hexamethylmelamine has shown no activity as a third-line drug to date.