An atypical human rotavirus strain Z10262, isolated from a chronically infected immunodeficient child, displayed an unusual genomic RNA electrophoretic pattern. Besides, Northern blot analysis indicated that this strain contained an abnormally migrating gene 11 equivalent. Sequencing of this gene showed that it was derived from a genetic rearrangement which involved a partial duplication of the open reading frame (ORF) encoding the non-structural protein NSP5. However, the duplicated region contained a deletion and several point mutations relative to the first copy of the ORF. Phylogenetic analysis of human and animal NSP5 amino acid sequences including Z10262 revealed two groups of human proteins related to different animal proteins. The isolation and analysis of Z10262 strain provides further evidence for the genetic complexity of naturally occurring human rotaviruses.