The use of oseltamivir,widely stockpiled as one of the drugs for use in a possible avian influenza pandemic,has beenreported to be associated with neuropsychiatric disorders and severe skin reactions,primarily in Japan.Here we identi-fied a nonsynonymous SNP(single nucleotide polymorphism)in dbSNP database,R41 Q,near the enzymatic active siteof human cytosolic sialidase,a homologue of virus neuraminidase that is the target of oseltamivir.This SNP occurredin 9.29% of Asian population and none of European and African American population.Our structural analyses and Kimeasurements using in vitro sialidase assays indicated that this SNP could increase the unintended binding affinity ofhuman sialidase to oseltamivir carboxylate,the active form of oseltamivir,thus reducing sialidase activity.In addition,this SNP itself results in an enzyme with an intrinsically lower sialidase activity,as shown by its increased Km anddecreased Vmax values.Theoretically administration of oseltamivir to people with this SNP might further reduce theirsialidase activity.We note the similarity between the reported neuropsychiatric side effects of oseltamivir and the knownsymptoms of human sialidase-related disorders.We propose that this Asian-enriched sialidase variation caused by theSNP,likely in homozygous form,may be associated with certain severe adverse reactions to oseltamivir. The use of oseltamivir, widely stockpiled as one of the drugs for use in a possible avian influenza pandemic, has been reported to be associated with neuropsychiatric disorders and severe skin reactions, among in Japan. Hepatology-fied a nonsynonymous SNP (single nucleotide polymorphism ) in dbSNP database, R41 Q, near the enzymatic active site of human cytosolic sialidase, a homologue of virus neuraminidase that is the target of oseltamivir. This SNP occurred in 9.29% of Asian population and none of European and African American population. Our structural analyzes and Kimeasurements using in vitro sialidase assays that that SNP could increase the unintended binding affinity of human sialidase to oseltamivir carboxylate, the active form of oseltamivir, thereby reducing sialidase activity. In addition, this SNP itself results in an enzyme with an intrinsically lower sialidase activity, as shown by its increased Km and created Vmax values with this SNP may further reduce theirsialidase activity. We note the similarity between the reported neuropsychiatric side effects of oseltamivir and the knownsymptoms of human sialidase-related disorders. We propose that this Asian-enriched sialidase variation caused by theSNP, likely in homozygous form, may be associated with certain severe adverse reactions to oseltamivir.