Cell surface expression of Ia antigens requires the assembly of alpha and beta heterodimers. We have produced a double transgenic mouse with a wild form Ak alpha gene and a mutant Ak beta (Ak beta MB) gene with d-allele substitution at positions 63 and 65-67. Initial studies indicated that the Ak alpha and Ak beta MB transgenes are not expressed on the surface of lymphoid cells of the transgenic mice. However, when spleen cells were stimulated with LPS prior to FACS analyses, Ak/Ak MB assembly and subsequent surface expression was induced. The tail skins from transgenic founder mice were rejected by the parental mice indicating a role for the mutant antigen on the allograft. In addition, the Ak transgenic mice on H-2q/q background can partially delete V beta 6+ T cells, suggesting the presence of the transgene product in the thymus.