In this study, we have assessed the efficacy of a nitrosourea, cystemustine, in treating patients with recurrent high grade glioma with overall survival analysis as primary end-point. Forty-eight patients with recurrent high grade glioma (24 glioblastomas, 17 astrocytomas and 5 oligodendrogliomas) were treated every 2 weeks with 60 mg/m2 cystemustine by a 15 min-infusion. The median number of treatment cycles was 4 (range 1-17). The median overall survival was 8.3 months (range 1-97) and the 6- and 12-month overall survival rates were 55.3% (95% CI, 41.3-68.6%) and 29.8% (95% CI, 18.6-44.0%), respectively. The objective response rate was 18.8% (95% CI, 7.7-29.9%), and 54.2% of patients had stable disease (95% CI, 40.1-68.3%). Multivariate analysis showed that WHO performance status, histology and response to cystemustine were significant prognostic factors for survival of patients with recurrent glioma. In conclusion, cystemustine has encouraging activity for patients with recurrent high grade glioma.