The effects of single agent therapy with 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea, 5-fluorouracil, and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide on a human malignant melanoma transplanted and passed serially in thymusless nude mouse were studied. Tumor response varied. A single dose of 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea induced initial tumor regression, but thereafter growth resumed at a rate similar to that in the untreated control animals. Wehn 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea was given in divided dosage at an interval of 8 days, marked and persistent tumor regression was observed. 5-Fluorouracil had no effect. Treatment with 5-(3,3 dimethyl-1-triazeno)-imidazole-4-carboxamide was always reflected by almost total regression of tumors, an effect that was independent of dose within the range tested in this study. The results resemble those reported from clinical practice in patients with disseminated malignant melanomas treated with the same agents. This suggests that the pattern of drug susceptibility is preserved after transplantation of tumors in the nude mouse. The human tumor-nude mouse system is advocated as a new in vivo model for determination of individual tumor response to chemotherapeutic agents, and its potential as a model for the proving of new chemotherapeutic agents is suggested.