The establishment of HLA transgenic mice as models for autoimmune disorders requires that the HLA molecules can be efficiently recognized and mediate positive and negative selection of mouse T cells. This question was investigated in DR3(DRw17) transgenic mice back-crossed to the B10.Q(H-2q) strain which does not form mixed mouse-human class II heterodimers. Here we report that efficient negative 5election on DR3(DRw17) molecules was observed for vβ5, 11, and 13 subpopulations of CD4+T cells, but not for vβ4, 7, 8, 9, and 10. vβ5 and 11 cells are also negatively selected by mouse class II E molecules which is the structural homologue to DR molecules. Positive selection on DR3(DRw17) was only observed for vβ6 cells but this was less efficient than positive selection of vβ6 cells by E molecules. The data indicate that DR3(DRw17) molecules select similar subgroups of mouse T cells as E molecules although with slightly different efficiency.