We sequenced the gene coding for the major neutralizing protein (VP7) from eight human rotavirus strains representing serotype 1, 2, 3, or 4. In addition, the corresponding gene of the rhesus rotavirus vaccine strain MMU 18006 (serotype 3) was sequenced. Comparative analyses of their deduced amino acid sequences revealed an overall 15-29% divergence in the VP7 proteins that define four different rotavirus serotypes and confirmed the presence of six discrete regions of clustered sequence divergence (amino acids 39-50, 87-101, 120-130, 143-152, 208-221, and 233-242). When the same regions were compared among rotaviruses belonging to the same serotype, a high degree of homology (91-99%) was detected. These observations indicate that differences in the serotype specificity among rotaviruses are the result of a high degree of sequence divergence in several discrete regions of the VP7 gene and that these regions are highly conserved within a given serotype.