The Ss-Slp region of the mouse genome is located between the two loci, H-2K and H-2D, of the major histocompatibility system. It controls the level of a serologically detectable serum globulin, the Ss protein, and its allotypic forms, Slp(a) and Slp(o). Evidence is presented that the Ss-Slp region is involved in control of the complement system. Mice of congenic resistant strains differing only at the H-2 gene complex show differences in complement levels. A comparison of H-2 recombinants demonstrated that complement level correlates with the Ss-Slp genotype and not with the H-2K, H-2D, or Ir genotypes. Among the 13 congenic strains tested, those with the Ss(h)Slp(a) allele had higher complement levels than those with the Ss(h)Slp(o) or Ss(l)Slp(o) alleles. Mice with recombinant H-2 haplotypes had complement levels similar to those of the parental strain that provided the Ss-Slp segment. It was also shown that anti-Ss serum inhibits complement activity of mouse serum in vitro.