A pilot study was performed administering PCNU with radiation therapy to treat patients with high-grade astrocytomas and to explore the toxic effects of this drug regimen. PCNU at an initial dose of 110 mg/m2 i.v. was administered to 14 patients within 4 weeks after completion of cranial irradiation. Courses were repeated every 6-8 weeks upon recovery from myelosuppression. Radiation therapy consisted of 5,000 rad to the whole brain followed by an additional 1,500 rad to the tumor site. Patients were followed by CT scan and neurologic examination. The median survival for the group was 80 weeks. Larger, randomized trials comparing PCNU to other nitrosoureas will be needed to assess its value as adjuvant therapy in patients with malignant gliomas. Myelosuppression, particularly, thrombocytopenia, was the main toxic effect in this study. Pulmonary infiltrates developed in 2 patients and was progressive and fatal in 1 patient after a total cumulative PCNU dose of 850 mg/m2. Hepatic dysfunction with hyperbilirubinemia also developed in 1 patient. PCNU can produce pulmonary and hepatic toxicity similar to that reported for other nitrosoureas. Regular monitoring of pulmonary and hepatic function tests should be performed during treatment with PCNU in future trials.