Sharks are members of the most primitive class of vertebrates (Chondrichthyes) shown to have an adaptive immune system. Suprisingly, however, class I genes have not been identified unambiguously in this taxon, and absence of class I loci or a failure to express class I genes might explain some of the relatively "weak" adaptive immune responses documented in cartilaginous fish. We report here the isolation of three unique cDNA clones from two different species of sharks that encode bona fide class I proteins. These clones exhibit different sequence and expression profiles indicating that they are likely to represent both classical and nonclassical class I lineages. In addition, our preliminary analysis suggests that there may be transfer of gene segments among shark class I genes over evolutionary time. The cloning of shark class I genes completes the identification of molecules that define the adaptive immune system (including Ig, TCR, and MHC class II proteins) in this taxon. Thus, simple models invoking a total absence of certain molecular hallmarks of the immune system to account for poor immune responsiveness in cartilaginous fish should be abandoned.