Phylogenetic relationships among 9 blood flukes (7 schistosome species, a spirorchid, and a sanguinicolid) were inferred from nucleotide sequences of the D1 domain of large subunit rRNA and the V4 region of small subunit rRNA. These sequences were more conserved than those examined by previous authors and thus may provide insight into deeper-level relationships. Analyzed separately and combined by 3 methods, these data yielded congruent trees that were well supported by bootstrap resampling. The traditional groups of schistosome species based on egg type were supported. Schistosoma japonicum and Schistosoma mekongi were distinct from the remaining Schistosoma species. Schistosoma spindale (from India and southeast Asia) clustered strongly with the African species to the exclusion of the other Asian species, S. japonicum and S. mekongi. Schistosoma spindale may have been brought to India and southeast Asia from Africa by early humans. Statistical tests revealed only weak evidence for the operation of a molecular clock in the V4 sequence; no evidence was found for this in the D1 domain.