Among T cell clones with specificity for cow insulin and autologous class II MHC products, a significant number displayed interesting patterns of alloreactivity to non-MHC antigens. Four clones are described in this report. One is a typical Mlsa-reactive clone, while the other three proliferate to a variety of allogeneic spleen cells with reportedly different Mls phenotypes. These include PL/J stimulator cells, designated Mlsx, all strains reported to be Mlsc, and several strains previously typed as Mlsa. Little is known about Mlsx except that it does not appear to be cross-reactive with Mlsa. In this report, therefore, we attempt to investigate the reasons why these clones seem to be stimulated by a variety of different Mls phenotypes. Our conclusions are, first, that some of the strains previously typed as Mlsa may actually express a second Mls product, either c or x, in a manner analogous to the CBA/J strain (which expresses both Mlsa and Mlsc), and second, that Mlsc and Mlsx are cross-reactive. In preliminary experiments, we investigate the genetic relationship between Mlsc and Mlsx by analysis of backcrosses, and the extent of cross-reactive recognition of Mlsc and Mlsx by raising T cell clones which recognize one but not the other. Our preliminary conclusion is that Mlsc and Mlsx are cross-reactive, but represent distinct gene products.