A review. A plethora of clin. syndromes are characterized by the deposition of amorphous, Congo red staining material known as "amyloid.". These protein folding diseases include Alzheimer's, Parkinson's, type II diabetes mellitus, rheumatoid arthritis, and "mad cow" disease. Amyloid-forming peptides readily adapt beta-sheet structure and can spontaneously aggregate into extended fibrils despite having no primary sequence homol. All amyloid peptides appear to interact strongly with lipid membranes, assemble into oligomers, and form ion-permeable channels. These channels are large, heterogeneous, nonselective, and irreversible. They are inhibited by Congo red and blocked by Zn+2. The leakage pathway induced by these channels could be responsible for the cellular pathol. of amyloidosis, including membrane depolarization, mitochondrial dysfunction, inhibition of long-term potential (LTP), and cytotoxicity. We suggest that channel formation underlies amyloid disease.