Abstract The saltwater crocodile (Crocodylus porosus) forms the basis of a crocodile farming industry for the international skin trade in Australia. For this industry, mortalities from stress and disease are common due to a compromise of the adaptive immunity. Currently the genetic understanding of the immune response is poor, which in turn impedes an understanding of genes, and hence genetic markers, affecting disease susceptibility. As a key component of adaptive immunity is the Major Histocompatibility Complex (MHC), this thesis characterises the MHC genes with an emphasis on the saltwater crocodile and assesses genetic diversity, evolutionary mechanisms that are influencing diversity and their roles in adaptive immunity. The genetic diversity among saltwater crocodiles showed the number of MHC variants within an individual ranging from one to seven, indicating that there are at least four gene loci in this species. An association between a certain MHC variant and Lymphoid proliferation/ Vasculitis/ Encephalitis in saltwater crocodiles was identified (P = 0.00007), suggesting genetic susceptibility to the disease. Phylogenetic analyses showed that MHC variants from 20 species of Crocodylia clustered at the genus or family level rather than in species-specific groups, indicating orthologous relationships. Selection detection analyses showed that balancing selection influenced some classes of MHC in Crocodylia. In addition, construction of Bacterial Artificial Chromosome scaffolds in the saltwater crocodile showed MHC class I genes located along with antigen processing genes and a framework gene. This would support structural variation of the saltwater crocodile MHC that differs from that expected in tetrapod ancestors. This project offers a better understanding of immunogenetics and immunogenomics in Crocodylia and presents recommendations for future research, where these findings could serve as a foundation in order to achieve a complete picture of MHC in Crocodylia.