Atlantic salmon (Salmo salar) cDNAs encoding the major histocompatibility complex (Mhc-Sasa) class II beta chain were isolated from a leucocyte library by a polymerase chain reaction (PCR) approach. Three different cDNAs (c144, c22, and c157) encoding the entire mature beta chain have been analyzed. Clone c144 differs from clone c157 in 12.6% of the nucleotides in the beta 1-encoding region. The corresponding differences between clones c144 and c22, and clones c22 and c157, are 10.3% and 5.2%, respectively. This variation is, at least in part, most likely attributable to allelism. The similarity indices between the highly conserved beta 2 domains from Atlantic salmon and corresponding sequences from humans (DQ beta), chicken (BL beta), carp (TLAII beta-1), and rainbow trout (O.M. No. 55) are 45%, 40%, 66%, and 97%, respectively. Variable residues in the beta 1 domains from Atlantic salmon correspond with polymorphic sites of beta 1 domains from higher vertebrates. The frequency of substitutions in the beta 1-encoding region exceeds that in the 3'-untranslated (UT) region with several folds, indicating extensive beta 1 polymorphism in Atlantic salmon.