In two consecutive trials, a total of 395 patients with ovarian cancer were treated with a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapeutic regimens including cisplatin or without this drug. With respect to neurotoxicity, 387 patients were fully eligible. The median follow-up for survival was 45 months. Neurotoxicity in any grade of severity developed in 47% of the patients treated with a cisplatin-containing regimen and in 25% of those treated with the non-cisplatin-containing regimen. The severity of neurotoxicity was much higher, however, in the cisplatin-treated patients. Neurotoxicity-free survival decreased below 50% at cumulative doses of cisplatin between 500 and 600 mg/m2. No additional effect of hexamethylmelamine on the incidence or severity of neurotoxicity could be demonstrated. In patients who survived for more than 5 years, the incidence of cisplatin neuropathy was 61%. Prognostic variables (age, International Federation of Gynecology and Obstetrics [FIGO] stage, performance status, and others) possibly associated with high-risk subgroups could not be identified. The only consistent factor correlated with neurotoxicity was the total dose of cisplatin received.