Old rats of the WAG/Rij strain have a high incidence (50%) of medullary thyroid carcinoma, a calcitonin (CT)-secreting tumor. We have characterized and quantified the topographical distribution of [125I]salmon calcitonin (sCT) binding sites in the kidneys of this strain, as compared to Wistar CF rats (2% incidence of spontaneous medullary thyroid carcinoma). We report here that, up to 15 days of postnatal development, the distribution of CT-binding sites in the kidney of the WAG/Rij strain was quite similar to that found in developing and adult Wistar CF rats. However, from the age of 1 month, sCT-binding sites were dramatically reduced in both the medulla and the inner part of the kidney cortex, though plasma CT levels were not significantly different in both strains. Adult WAG/Rij rats bearing a transplanted tumor for 12 weeks had a high level of plasma calcitonin and exhibited an even greater reduction of both medullary and cortical sCT-binding sites. These results suggest that the modification in the CT-binding sites in WAG/Rij rats is not a consequence of a possible down regulation due to elevated circulating hormonal level but could be inherited and possibly associated with the later development of the tumor in this strain.