Twenty-three patients with oat cell cancer of the lung were randomized to receive chemotherapy with POCC (procarbazine, 100 mg/m2 per day orally, days 1-11; vincristine, 2 mg i.v. days 1 and; cyclophosphamide, 600 mg/m2 i.v. days 1 and 8; and CCNU [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea], 60 mg/m2 orally, day 1) or COM (cyclophosphamide, 2000 mg/m2 i.v. day 1: vincristine, 2 mg i.v. day 1 and methotrexate, 30 mg/m2 i.v. day 15). After 2-3 cycles of chemotherapy, all patients were to receive radiotherapy to initially involved sites and then have chemotherapy continued. Patients treated with POCC had a median survival of 11 mo. vs. 10 mo. for those treated with COM (P = 0.055). Eight of 15 1st sites of relapse were intrathoracic and 5 of these 8 received radiotherapy to that site. Six CNS failures were evenly divided between the 2 chemotherapy programs. CNS penetration of procarbazine and CCNU in the POCC combination did not prevent CNS relapse. All future patients will receive prophylactic brain radiotherapy.