Scrapie belongs to a group of diseases called transmissible spongiform encephalopathy (TSE) diseases and appears in sheep and goats. Other diseases of this group include bovin spongiform encephalopathy (BSE) disease in cows and Creutzfeldt-Jacob disease (CJD) in humans. Scrapie is associated with the accumulation of an abnormal isoform of prion called scrapie prion protein (PrP sc ) in nerve cells. The normal form of this prion is called cellular prion protein (PrP c ). The polymorphs existing in the scrapie gene play a role in manifestation of the disease and susceptibility to it. There are different polymorphs in the scrapie gene of which those in the three codons 136, 154 and 171 are more important for susceptibility to scrapie. Different scrapie strains affect animals differently based on the polymorphs existing in the scrapie gene. Thus, the genotype VV 136 -- 154 -- 171 shows the highest susceptibility to the strain /1, whereas the genotype AA 136 RR 154 QQ 171 has high susceptibility to the strain CH1641. The genotype AA 136 RR 154 RR 171 is resistant to both scrapie strains. One hundred and fifty blood samples were collected from the three breeds of Naeini, Lori Bakhtyari and Zandi sheep and studied in order to identify the susceptible codons to scrapie. DNA extraction from blood samples was done through the modified salting out method. In order to study polymorphs in the codons in question, the PCR-RFLP method was applied. For this purpose, two PCR reactions were designed: one for the study of polymorphs in codons 136 and 154 and another for the study of polymorphs in the codon 171. At the PCR-RFLP stage, the enzyme PagI was used to study the polymorphs of codons 136 (Alanine, A/ Valine, V) and 154 (Histidine, H/ Arginine, R) and the enzyme BclI to study the polymorphs of the codon 171 (Glutamine, Q/ Arginine, R). The results of the study showed that the highly scrapie-susceptible genotype AA 136 RR 154 QQ 171 in the two breeds of Naeini and Zandi had the highest frequency (62% and 72% respectively) of all the genotypes. As for the Lori Bakhtyari breed, the genotype AA 136 HH 154 QQ 171 had the highest frequency (60%). However, the frequency of the highly susceptible genotype VV 136 -- 154 -- 171 in all three breeds and that of the susceptible genotype AV 136 -- 154 -- 171 in the Lori Bakhtyari were zero. The Lori Bakhtyari showed no polymorph in the two codons 136 and 171 where A and Q were the only alleles respectively. The completely resistant genotype AA 136 RR 154 RR 171 had not been seen in any of the breeds. The results of this study will constitute an advantageous background for further studies on