Fotemustine is a third-generation nitrosourea characterized by a phosphoalanine carrier group grafted onto the nitrosourea radical, which gives it a high lipophilicity and a better penetration through the cell membrane. Between September 1988 and December 1997, 22 patients with inoperable or incompletely resected recurrent high-grade gliomas of the brain were treated at the University Hospital in Brest (France). Treatment consisted of three weekly infusions of fotemustine (100 mg/m2 days 1, 8 and 15). If patients responded or were stabilized, fotemustine was continued at the same dose, but every three weeks only. Four patients responded to the treatment (18%), while 6 were stabilized (32%). Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia); treatment was only interrupted in one patient for leucothrombopenia, and there was no toxic death. Medium duration of response and/or stabilisation was 6.5 months, and median survival 9.4 months in responding and/or stabilized patients, while it was only 5.0 months if tumour progressed under chemotherapy (median survival for all patients: 7.5 months). Besides, there was a difference in survival in favour of the young patients (< 50 years-median survival = 11.8 months) in comparison with patients between 50 and 60 years (median survival = 6.8 months; p = 0.0282) or elderly patients (> 60 years-median survival = 5.8 months; p = 0.0634). In our series, we did not found any difference in survival according to the initial performance status of patients before treatment. Therefore, fotemustine seems to represent an interesting well-tolerated treatment possibility in patients with inoperable recurrent malignant gliomas of the brain.