Background: Gliomatosis cerebri (GC) is a diffuse infiltrating glial tumor with involvement of at least 3 cerebral lobes. There are only few data on the efficacy of initial chemotherapy in patients with GC. Patients and Methods: In 3 neurooncological centers, patients with newly diagnosed GC who had received procarbazine (60 mg/m(2), days 8-21/56) and CCNU (110 mg/m(2), day 1/56) chemotherapy (PC) as initial treatment were analyzed for progression-free survival, overall survival and toxicity. Results: Twelve patients (median age 46 years, range 27-72) were analyzed. The median progression-free survival and the median overall survival were 16 and 37 months. Grade 3 or 4 hematotoxicity was observed in 3 of 12 patients (25%). Conclusions: These data support the efficacy of PC chemotherapy in newly diagnosed GC. Initial PC chemotherapy should be considered as a treatment option and evaluated in larger clinical trials.