The dodecaploid anuran amphibian Xenopus ruwenzoriensis represents the only polyploid species of Xenopus in which the full silencing of the extra copies of the major histocompatibility complex (MHC) has not occurred. Xenopus ruwenzoriensis is a recent polyploid that has evolved within one of the two tetraploid groups of Xenopus through allopolyploidization. Family studies of its MHC haplotype suggested a polysomic inheritance of the MHC class I and II genes. Four class Ia bands can be detected per individual in Southern blot analysis and, similarly, four different cDNA sequences are expressed per individual. The Xenopus class Ia sequences we analyzed belong to only one of the old class I lineages and show a homogenization of their alpha3 domain sequences. This homogenization occurred after speciation within the Xenopus ruwenzoriensis species, either due to gene conversion or inter-alleles/loci recombination.A re-evaluation of the polymorphism of class Ia in Xenopus, by looking at the rate of non-synonymous versus synonymous substitutions, suggests that Xenopus MHC class Ia genes are not under strong overdominant selection. This is a rare situation among vertebrates. The observed polymorphism is most likely due to the interlocus genetic exchanges related to the peculiar mode of speciation of the genus.