S100 protein is a low molecular weight calcium-binding protein widely distributed in the central nervous system of vertebrates. Recent evidence suggests that S100 protein may play a role in the regulation of glial proliferation and neuronal differentiation. The gene for S100 protein has been mapped to the 21q22 region, a chromosomal locus whose duplication has been implicated in the generation of Down Syndrome (DS). This raises the possibility that abnormalities in S100 protein gene dosage at a critical period during development may be responsible for some of the neurologic abnormalities associated with DS.