The burden imposed by disease recurrence in patients with high-grade gliomas is not well documented. We studied the frequency of self-report symptoms and the effects on health-related quality of life in patients who had recurrent glioblastoma multiforme or anaplastic astrocytoma and who had a Karnofsky performance score > or = 70. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (QLQ-C30) and the Brain Cancer Module (BCM20) before initiation of treatment for first recurrence of disease. Six symptoms (fatigue, uncertainty about the future, motor difficulties, drowsiness, communication difficulties, and headache) were reported with a frequency > 50% by both groups of patients. An additional two symptoms (visual problems and pain) were also reported with frequencies of > 50% by patients with recurrent glioblastoma multiforme. Most of the symptoms were likely due to recurrence, but previous radiation therapy and on-going corticosteroid treatment may have also been casual factors for fatigue, whereas uncertainty about the future and pain were probably nonspecific for brain cancer. Problems with motor functioning, vision, leg strength, and pain were reported more frequently by patients with recurrent glioblastoma multiforme than by those with recurrent anaplastic astrocytoma. Scores on health-related quality-of-life functioning scales were similar in the two groups. Finally, the scores for patients who had recurrent high-grade gliomas and a Karnofsky performance score > or = 70 were compared with the reported health-related quality of life scores of patients with other cancers. Their scores were similar to those of patients with metastatic cancers and worse than those of patients with localized cancers.