Previous studies of associations of metabolic polymorphisms with the occurrence of malignant brain tumors have suggested that there is a significantly increased risk of development of adult gliomas in individuals who carry a poor metabolizer CYP2D6 variant allele and the GSTT1 null genotype. To investigate this further, a population-based case control study of adult glioma in the San Francisco Bay area was conducted. Patients (n = 188) diagnosed with brain tumors and controls (n = 166) were enrolled using random digit dialing and were frequency matched for age, ethnicity and gender. Genotyping for the polymorphisms was performed using standard PCR-based techniques. The analysis of the data was restricted to Caucasians because the prevalence of these traits is known to vary by ethnicity. No overall association of either the GSTT1 null genotype or CYP2D6 homozygous variant PM genotype was observed with the occurrence of brain tumors. However, when stratified by histopathologic subtype, there was a significantly increased risk for oligodendroglioma associated with the GSTT1 null genotype, with an OR of 3.2 (95% CI 1.1-9.2). These data suggest that the GSTT1 polymorphism may play a role in the development of a subset of malignant brain tumors in adults, and indicate the need for further studies.