Summary: The first teleostean MHC sequences were described for carp. Subsequent studies in a number of cyprinid fishes showed that the class I sequences of these fishes are of particular interest. Two distinct lineages (Cyca-Z and Cyca-U) are found in the common and ginbuna crucian carp, but only the U lineage is present in zebrafish and other non-cyprinid species. The presence of the Z lineage is hypothesised to be the result of an allotetraploidisation event. Both phylogenetic analyses and amino acid sequence comparisons suggest that Cyca-Z sequences are non-classical class I sequences, probably similar to CD I. The comprehensive phylogenetic analyses of these sequences revealed different phylogenetic histories of the exons encoding the extracellular domains. The MHC genes were studied in laboratory and natural models. The natural model addressed the evolution of MHC genes in a Barbus species flock. Sequence analysis of class I and class II supported the species designation of the morphotypes present in the lake, and as a consequence the trans-species hypothesis of MHC polymorphism. The laboratory model involves the generation of gynogenetic clones, which can be divergently selected for traits such as high and low antibody response. The role of MHC molecules can be investigated further by producing a panel of isogenic lines.