Genetic control of PQ prolongation of the electrocardiogram (ECG) in the mouse, immunized with killed group A streptococci, was studied by using various congenic mice. Mice of H-2a, H-2k and H-2f haplotypes showed high frequencies of PQ prolongation, while haplotypes of H-2b, H-2d and H-2s showed low frequencies of PQ prolongation. Studies using various recombinant mice revealed that at least one immune-associated (Ir) gene mapped in the left side of the I-B subregion. High responsiveness of F1 hybrids of H-2b and H-2d, as well as B10.A(5R) and B10.A(3R), suggests the existence of a complementing gene. In addition, the differences between C3H and CKB, as well as differences between C3H.SW and CWB, indicate that another Ir gene maps in the immunoglobulin heavy chain (Igh) coding loci. Repeated injections of anti-I-J or anti-I-A antisera also modified this PQ prolongation. These results suggested that both the major histocompatibility complex (MHC) and immunoglobulin (Igh) loci seem to be playing important roles in the pathogenesis of PQ prolongation.