Scrapie is a prion disease that affects the sheep and goats. It belongs to the group of transmissible spongiform encephalopathies (TSE). TSEs are characterized by the accumulation of the pathological form (PrPSc) of the cellular prion protein (PrPC). The susceptibility of sheep to scrapie is influenced by polymorphisms in the PrP gene (PRNP). The aim of this study was to identify the genetic variability of sheep PRNP in Algerian sheep. Two-hundred and thirteen Algerian sheep from eight breeds (Ouled Djellal, Rembi, Hamra, Berbere, Barbarine, Sidaou, Taadmit and Tazegzawt) with no clinical manifestation of scrapie were analysed. Sequencing of the entire coding sequence of PRNP showed four main alleles (ARQ, ARR, AHQ and ARH) based on codons 136, 154 and 171 with different frequencies among the investigated breeds. Moreover, 14 additional nonsynonymous polymorphisms (Q101R, N103K, M112T, A116P, M137I, L141F, I142M, H143R, N146S, R151G, Y172D, N176K, H180Y and S240P) as well as two synonymous polymorphisms at codons 231 and 237 were found in the PRNP gene. Interestingly, the N103K, M137I and I142M polymorphisms were not described in sheep. The ARQ, ARR and ARH haplotypes were present in all breeds with a highest frequency of ARQ in Barbarine. The ARH was absent in Barbarine breed and the VRQ haplotype was absent in all Algerian breeds studied. The ARQ and ARR alleles were the most common with frequencies ranging from 30 to 65% and from 8 to 26%, respectively, in different breeds. These results represent the first study on PRNP variability in Algerian sheep and may serve as a basis for the development of breeding programmes to render national sheep breeds resistant to scrapie.