The effect of the genetic background on the distribution and excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in two sets of congenic mouse strains in which the congenic pairs differed only at the Ah locus. Male C57BL/6J mice which were either Ahb/Ahd or Ahd/Ahd and female DBA/2J mice which were also Ahb/Ahd or Ahd/Ahd were treated with 500 ng/kg 3H-TCDD and held from 1 to 42 days in individual metabolism cages. Daily excretion and tissue distribution at eight time points were determined. The Ah locus had no effect on the distribution of TCDD-derived radioactivity to the major tissue depots of adipose tissue, skin, kidney, carcass, and blood but seemed to cause elevated levels in the liver. The Ah locus also played no role in either the rate or the extent of urinary and/or fecal excretion. However, the route and rates of excretion did vary between the congenic sets with the male C57BL/6J mice excreting greater amounts of radioactivity in the urine and less in the feces than the female DBA/2J mice. The Ah locus also had no effect on the liver weight or adipose tissue volume in either congenic set. Thus, at the dose level studied, the distribution and excretion of TCDD were primarily governed by the total genetic background rather than the allele present at the Ah locus.