The immunohistochemical distribution of S-100 beta protein in patients with Down's syndrome was investigated as part of a study aimed at ascertaining a possible involvement in the syndrome (trisomy 21) of this protein, which has recently been shown to be coded in chromosome 21. No appreciable differences in the cell distribution of the antigen could be observed between patients with Down's syndrome and normal subjects. The possibility of an overexpression or abnormal expression of the molecule as a consequence of chromosome 21 triplication, not detectable by immunocytochemical methods alone, remains to be investigated.