Serotonergic (5-hydroxytryptamine; 5-HT) transmission has been implicated in the pathogenesis of Alzheimer's disease (AD). A coding single nucleotide polymorphism 267 (C/T) in the 5-HT(6) receptor gene was previously reported as a susceptibility factor for AD. An extensive replication study was performed using our data set including sporadic and familial cases. No significant association between the 5-HT(6) receptor gene and AD was obtained with or without the stratification of apolipoprotein E epsilon 4 status. Our result suggests that the 267C allele of the 5-HT(6) receptor gene may not be a genetic risk factor for AD.