A total of 14 men with inoperable or metastatic squamous cell carcinoma of the genital tract received methotrexate, bleomycin and cisplatin. In 12 patients the penis was the primary site. Metastases were usually advanced, and 4 patients had ulceration and infection in the inguinal region or perineum secondary to tumor. Two patients had tumor-related hypercalcemia. Of the patients 11 received the 3 drugs intravenously, whereas 3 received methotrexate intravenously, and bleomycin and cisplatin intra-arterially for large unilateral nodal metastasis. Of the 14 patients 10 responded, for a response rate of 72% (95% confidence interval 57 to 92%) and the median response duration was 6 months (range 4 to 24 months). Two patients (14%) who were treated intravenously achieved complete responses lasting 6 and 24+ months. Responses occurred in 3 patients with infection and in both patients with hypercalcemia. The combination of methotrexate, bleomycin and cisplatin has significant activity in patients with advanced squamous cell carcinoma of the male genital tract. This chemotherapy regimen should be evaluated in earlier disease in the adjuvant or neoadjuvant setting.