This review has been directed towards those aspects of DS which bear upon pathological aging. Clinical dementia in DS has heretofore been studied largely by retrospective methods with variable findings. A prospective study utilizing techniques designed to measure cognitive performance in a poorly verbal, retarded population is badly needed. There is definitive evidence for Alzheimer's disease changes in the brains of DS patients with some suggestion of altered topography compared to the general population. Immunological studies have established a T-cell deficiency in DS that may be linked to precocious aging of thymic-dependent processes. Both antiviral and nonantiviral effects of interferon are accentuated in cell culture systems utilizing DS tissue, presumably as a consequence of the localization of the interferon gene(s) on chromosome 21. Multiple endocrine studies confirm the high frequency of autoimmune disease, an abnormality that may be related to the problems of immune surveillance in DS. Precocious aging has been noted in regards to measures of skin elasticity, fenestration of cardiac valves, and premature cataracts. The 21st chromosome has been implicated in the elevated activity of superoxide dismutase, a finding of significance in regard to potential intracellular damage from increased levels of peroxide. Several studies have suggested a compensatory increase in glutathione peroxidase.