Clinical chemotherapy in the treatment of neuroblastoma is undergoing further evaluation. Chemotherapeutic agents, cyclophosphamide, vincristine, and hexamethylmelamine, were investigated in a murine neuroblastoma model that, in part, histologically and morphologically resembles the human tumor. The tumor was inoculated subcutaneously (SC), intramuscularly (IM), intraperitoneally (IP), intrarenally (IR). Growth of tumor was observed at all sites, as well as the appearance of metastases. Maximal survival of 32 +/- 1 days was seen (SC) and the minimum was 15 +/- 1 days (IR) (p less than 0.05). Corresponding survival rate for IM was 26 +/- 1 days and IP 21 +/- 1 days. For this reason SC was selected for drug testing. Cyclophosphamide 100 mg/kg/week showed the most favorable results, as determined by autopsy status with fewer tumors and a greater tumor weight decrease over time. This agent also showed a significantly longer survival in comparison to all other drugs (p less than 0.0001). The results with vincristine and hexamethylmelamine in the dose ranges employed differed little from the placebo, except for the finding of a slight decrease in body weight at autopsy.