Nothing is known about the pathophysiology of sudden infant death syndrome (SIDS). Here we show the presence of misfolded prion protein (PrP(Sc)-like) in extracts of various sections of the brains of two SIDS victims. DNA sequence information for one of these (death at 12 days) revealed two nucleotide variants in the protein coding region of the PrP gene. This may be a key finding in the understanding of SIDS pathology, and may suggest ways for identifying risk factors for SIDS in newborn infants.