Toxicity of the prion protein-derived peptides is independent of amyloid formation. Toxicity of mPrP1-28 and bPrP1-30 is due to oligomeric or non-fibrillar assemblies. Toxicity of the peptides is attributed to plasma membrane perturbation. Low pH inhibits ordered aggregation of the peptides and abrogates their toxicity. Under non-toxic conditions, the peptides accumulate in late endosomes/lysosomes.