The Northern California Oncology Group (NCOG) conducted a nonrandomized phase II study to evaluate the benefit of a seven-drug chemotherapy protocol (NCOG 6G91) in patients with glioblastoma multiforme (GM). Time to tumor progression was the primary end point of the study. The treatment consisted of 5-FU and lomustine administered after surgery and before radiation therapy, hydroxyurea and misonidazole during radiation therapy, and procarbazine and vincristine alternated with carmustine and 5-FU after radiation therapy. Ninety patients entered the study; data from the 64 patients with GM who completed radiation therapy and at least started the postradiation chemotherapy regimen and returned for follow-up examination are analyzed in this report. The median time to tumor progression in the 64 adequately treated patients was 42 weeks; the 25th percentile value was 60 weeks. A Cox multivariate analysis showed that age and extent of surgical resection were important prognostic variables in patients with GM. The results of this treatment regimen were similar to those of a previous NCOG protocol (6G61), which consisted of hydroxyurea during radiation therapy followed by chemotherapy with carmustine or a combination of lomustine, procarbazine, and vincristine.