Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes.