We compared sequential single-agent BCNU and procarbazine (PCB) chemotherapy in 31 patients with gliomas [grade IV (10), grade III (15), grade II (6)]. Patients had failed surgical biopsy +/- resection and radiation therapy. All patients were treated initially with BCNU 150-300 mg/m2 by intra-arterial or intravenous route every 6 weeks. After CT evidence of tumor progression, all patients received PCB 150 mg/m2/day for 28 days every 8 weeks. Patient responses to BCNU were CR (0), PR (7), SD (12), progression (12), and to PCB CR (2), PR (9), SD (6), and progression (14). Kaplan-Meier estimates of median time to failure for all patients were shorter for BCNU, 5.0 months (range 1.5-20), than for PCB, 6.0 months (range 2-50+). There was a statistically significant difference (Mantel-Cox test, p = 0.02) in the distribution of time to disease progression between the two drugs, especially for grade III tumors (p = 0.02). The cumulative proportion of patients without disease progression at 6 months was 26% while on BCNU, compared to 48% while on PCB; at 12 months the cumulative proportions were 3% for BCNU compared to 35% for PCB. Although there was no formal washout period between administration of the two drugs, no carryover effect was evident. These data provide further evidence that PCB has significant activity against malignant glioma and may, in fact, be more effective than BCNU.