The purpose of the study was to assess health-related quality of life (HQL) in patients with high-grade malignant glioma of the brain. The EORTC core Quality of Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered at baseline and several weeks later (follow-up) to 105 patients with either recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition, the attending neurologists completed a standard neurological examination, a modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have acceptable reliability (internal consistency and test-retest reliability). Newly-diagnosed patients and those with a KPS of 80-100 had significantly better physical, role and cognitive functioning and global quality of life with less fatigue, visual disorder, motor dysfunction, communication deficit, weakness of both legs and trouble controlling the bladder than did those with recurrent disease and those with a KPS of 50-70. Similarly, those capable of independent activities of daily living, as reported on the BADLI, had higher functioning scores and less fatigue than did those who were not independent. Patients with dysphasia, mental confusion or motor deficit on neurological examination reported significantly lower levels of physical, role, cognitive, emotional and social functioning and global quality of life than did patients not having these difficulties. They also had significantly more symptoms. In patients with deteriorating neurological status between baseline and follow-up, there was a marked decline in cognitive, physical, role, emotional and social functioning and global quality of life and an increase in fatigue. Thus, there are significant differences in HQL between patients with newly-diagnosed and recurrent brain cancer and between patients with differing KPS and BADLI scores. In addition, the HQL scores provide details not provided by the KPS and the BADLI. Deterioration in neurological function is accompanied by significant deterioration in a range of HQL domains and in global quality of life.