Advanced cancer of the testis was treated in 36 patients with different combinations of an alkylating agent, an antimetabolite, and the antitumor antibiotic actinomycin D. Of 23 patients treated with the three classes of drug in combination, 12 gave evidence of tumor regression. Of 9 patients treated with an alkylating agent and actinomycin D, 2 showed resolution of pulmonary metastases. Of 8 patients treated with 6-mercaptopurine (6-MP) and 6-diazo-5-oxo-L-norleucine (DON), one responded. Of the 15 respondents, 10 had choriocarcinoma with or without embryonal carcinoma and teratocarcinoma or both. Tumor regression was associated with a fall of urinary chorionic gonadotropin titer. Side-effects occurred but proved reversible, and they were accepted as hazards of the treatment because of the striking improvement obtained in some cases.