Prion diseases are fatal neurodegenerative disorders in which an abnormal isoform of prion protein (PrPSc) accumulates in brain. Prion disease is either inherited as an autosomal dominant disorder with very high penetrance, sporadic, where no epidemiological association with other human or animal prion diseases can be demonstrated or acquired, where disease results from contamination with PrPSc from another case of prion disease. No human case of prion disease is known to have been acquired from an animal but about 50 cases have been acquired from contaminated growth hormone or gonadotrophin prepared from human pituitaries, from human meningeal transplants or other neuro-surgical procedures. Several thousand cases of the prion disease, kuru, occurred in Papua New Guinea, mainly during the first half of this century. This epidemic probably started with a sporadic case of Creutzfeldt-Jakob disease but was transmitted through funerary practices which are though to have involved endo-cannibalism. Inherited cases of prion disease are associated with mutations in the PrP gene. There are at least five point mutations and a further five mutations involving five to nine extra repeats of the five octapeptide repeat sequence in the PrP gene, all of which may lead to one of the forms of human prion disease i.e. Creutzfeldt-Jakob disease, Gerstmann-Sträussler syndrome and atypical prion dementia. In addition there is a common polymorphism at codon 129 of the PrP gene. This may affect age at onset and duration of illness in inherited and sporadic cases.(ABSTRACT TRUNCATED AT 250 WORDS)