The trilateral co-operative research initiative described here seeks to utilize new molecular based assays to study the immune response of children with natural rotavirus infections in South India. A birth cohort of 350 children in Vellore will be monitored for a total of 3 years. Antibody responses to structural proteins of rotavirus (VP7, VPT*, VP8* and VP6) and to the viral enterotoxin, NSP4 will be evaluated in enzyme-linked immunoassays, using individual antigens expressed in baculovirus or as fusion-proteins in bacteria. Antibody assays will be carried out in parallel on fecal and serum samples obtained in the acute and post-infection phase of symptomatic illness and also in asymptomatic infection. These studies will enable us to determine whether antibodies to a particular protein or combination of proteins can serve as a correlate of protection from rotaviral disease, in a setting where genetically diverse rotaviruses circulate. With the withdrawal of the only licensed rotaviral vaccine, it is imperative that a correlate of protection be identified in order to design subunit vaccines and to assess the efficacy of vaccines in future trials.