Cell surface expression of class 11 major histocompatibility complex encoded (1a) molecules depends on association of the component alpha and beta chain into a stable heterodimer. Studies on cell lines transfected with MHC class II genes have revealed important limitations on the assembly of haplotype-mismatched A alpha:A beta complex. In order to study alpha:beta chain pairing restrictions in vivo a number of lines of transgenic mice carrying the A alpha k gene were generated. The transgene was studied in the context of H-2b, H-2s, H-2q, H-2u, H-2f and H-2v haplotypes. Initial FACS analysis of spleen and peripheral blood cells showed no A alpha kappa expression. Spleen cells stimulated with LPS and analysed by FACS showed A alpha k expression in three different H-2b strains as well as H-2u, but not in others. These data indicate that A alpha k can associate with A beta b and A alpha k, but not with A beta s, A beta q, A beta f, A beta v.