The H-2 region in the mouse and the analogous major histocompatibility regions in other species have been shown to be genetic regions which control immunological responsiveness to a number of immunogens. Nevertheless, other less obvious genetic complexes which regulate immunological functions for a number of immunogens could also exist. The Ir-3 gene is an example of a non-H-2 linked immuneresponse gene which controls responsiveness to the synthetic polypeptide (T,G)-Pro--L. SJL/J mice are the lowest responders to (T,G)-Pro--L, whereas DBA/1 mice are the lowest responders. The purpose of the present study was to establish whether a genetic region can be identified in the mouse other than H-2 which regulates multiple immunological function and responsiveness to a variety of immunogens.