Multiple avenues of research have provided evidence for the role of genetic and environmental factors in epilepsy. Previous studies indicated an association of debrisoquine hydroxylase (CYP2D6) with susceptibility to epilepsy. In this study, association of CYP2D6 100C > T and 2850C > T polymorphisms with generalized tonic clonic seizures (GTCS) among Indians has been analysed using case-control approach. A significant association of 2850C > T (P = 0.015) has been observed. Comparison between phenytoin toxic and others among patients showed no association of these polymorphisms with phenytoin toxicity.