BCNU has an established role in the treatment of high-grade gliomas and has previously been used as first line therapy for recurrent disease. More recently, Temozolomide has taken its place as first line therapy for recurrent high-grade glioma. Thus, BCNU has become our standard second line therapy following disease progression after Temozolomide therapy. This study retrospectively analysed the activity and toxicity associated with BCNU as second line therapy. Twenty four patients with recurrent high-grade gliomas were treated with BCNU having previously received Temozolomide. Patients received BCNU intravenously at 130-200 mg/m2 every 6 weeks. The median number of treatment cycles was two (range 1-8). Of the 24 patients, one patient (4%) achieved a partial response and six (25%) achieved a minor response or stable disease. BCNU was generally well tolerated. In conclusion, BCNU has limited activity as second line chemotherapy following the use of Temozolomide. Novel strategies are required in this patient group.