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 selection on DR3(DRw17) molecules was observed for v beta 5, 11, and 13 subpopulations of CD4+T cells, but not for v beta 4, 7, 8, 9, and 10. v beta 5 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 v beta 6 cells but this was less efficient than positive selection of v beta 6 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.