Three patients with MEN IIA S belonging to the same family, which has five affected subjects in two generations, have been studied. Constitutional karyotype examination identified an extra ring chromosome in 3% of the cells in one of the affected subjects. The number of rings for each cell varied, and different evolutionary aspects of the ring, such as doubling and interlocking, were present. Furthermore, asynchronous DNA replication of doubling rings was observed. This nonhomogeneous, nonrandom chromosome abnormality found in normal tissue of patients with MEN IIA S could be indicative of sensitivity to structural alteration of some chromosome regions.