Methotrexate, bleomycin or cisplatin was used to treat 21 patients with advanced bidimensionally measurable epidermoid carcinoma of the penis. Patient characteristics were similar in all 3 drug trials. Drug therapy was continued with each agent until the disease progressed. Significant tumor regression was observed in 8 of 13 men (61 per cent) treated with methotrexate, 3 of 12 (25 per cent) treated with cisplatin and 3 of 14 (21 per cent) treated with bleomycin. Responders tended to be younger than nonresponders (median age 48 versus 59 years, respectively, p less than 0.05) and lived a median of 8 versus 2 months, respectively (p equals 0.03). Cross-resistance was not encountered among the 3 drugs. Future trials might investigate combination regimens of all 3 agents.