One patient of a French family with Gerstmann-Sträussler-Scheinker syndrome with the mutation in codon 117 of the prion protein (PrP) gene displayed unexpected neuritic degeneration around PrP plaques and numerous diffuse neurofibrillary tangles, whereas other members did not. The tau profile in this patient's brain was analysed and compared with one from another member of the Gerstmann-Sträussler-Scheinker family as well as with the Alzheimer's tau profile. A panel of well characterised antibodies against both normal tau protein and paired helical filaments-tau protein was used on immunoblots of brain proteins resolved by mono and two dimensional gels. The tau profile in the patient with Gerstmann-Sträussler-Scheinker syndrome without neurofibrillary tangles was normal. The tau profile from the patient with Gerstmann-Sträussler-Scheinker syndrome and neurofibrillary tangles was characterised by a hyperaggregation state of tau protein. This case illustrates the phenotypic heterogeneity of the GSS117 mutation not only from one family to another, but also between members of the same family. In this family, the presence of neurofibrillary tangles is still unexplained, but could be correlated with either the protracted duration of the disease or the old age of the patient.