Compelling evidence suggests that cerebral deposition of aggregating beta-amyloid protein may trigger the neurodegenerative cascades of Alzheimer's disease, Down syndrome, and, to a lesser degree, normal aging. We propose further that free oxygen radicals are critically involved in beta-amyloidosis. Apart from the established role of free radicals in other amyloidoses, our proposal is consistent with a large number of findings. Among these are (a) the salient relationship of Alzheimer's disease with aging and the increase in free oxygen radical liberation with advancing age; (b) biochemical and analytic epidemiologic evidence that free radical formation is increased in the disorder; (c) preliminary evidence that quenching free radicals slows the clinical progression of Alzheimer's disease; (d) the early and invariable beta-amyloid accumulation in trisomy 21, a syndrome associated with elevated free radical activity and with concomitant high levels of beta-amyloid precursor protein; (e) other factors that may be associated with increased liberation of free oxygen radicals and deposition of beta-amyloid protein. Possible mechanisms by which free radicals might modulate beta-amyloidosis are discussed.