Alterations of glycine receptor alpha1 and beta subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3'-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3'-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n = 104) and a control group (n = 141). The genotype frequencies for exonic and 3'-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n = 104) and an ethnically matched control group (n = 141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders.