Expression of human leukocyte antigens (HLA) is important for the immune response against infectious agents and malignant cells. Association of single HLA antigens or HLA haplotypes with disease has been investigated previously, and positive correlations between HLA and some cancers, such as cervical or nasopharyngeal carcinomas have been reported. In the present study, HLA antigen frequencies of 65 adult Caucasian patients with low-grade, anaplastic, or malignant astrocytic glioma (WHO grades II - IV) were compared with 157 racially similar, asymptomatic control individuals. Standard serologic (NIH) and PCR (-SSP) techniques for HLA typing were employed. Our results suggest a positive association between single HLA antigens and presence of symptomatic cerebral glioma. Compared with the control population, patients positive for HLA-A*25 had a 3.0-fold increased risk of glioma (p=0.04), patients positive for HLA-B*27 a 2.7-fold risk (p=0.03), and patients positive for HLA-DRB1*15 a 2.2-fold risk (p=0.03), whereas HLA-DRB1*07 was associated with a 0.4-fold decreased risk of glioma (p=0.02). Occurrence rate of some HLA antigen combinations and estimated haplotypes was also different in glioma patients. Thus, HLA-DRB1*15:DRB5*(51) expression in combination with HLA-DRB1*11 expression was associated with a 13.4-fold increased risk of glioma (p=0.01), and HLA-Cw*06:DRB1*07 expression with a 0.2-fold decreased risk of glioma (p=0.03). In conclusion, single HLA antigens and their combinations and estimated haplotypes are possibly significantly more or less frequent in persons developing cerebral glioma during their adult life, compared with asymptomatic individuals.