Scrapie (SC) is a transmissible spongiform encephalopathy (TSE) in sheep and goats. Susceptibility to this neurodegenerative disease is controlled mainly by point mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to modulate resistance/susceptibility to SC. On the basis of several studies on Alzheimer's disease and different TSE models, and of requirement for correct homeostasis of cytokines in brain, IL1B and IL1RN were chosen as putative positional and functional candidate genes that might be involved in the polygenic variance mentioned above. In the present work, ovine IL1B and IL1RN genes were partially isolated and characterized, including promoter and other regulatory regions. In addition, several sequence polymorphisms were identified. Furthermore, their cytogenetic positions on sheep chromosomes were determined by FISH and confirmed by linkage analysis, localizing both genes in OAR3p22, a region previously described as carrying a QTL for SC incubation period in sheep. Finally, expression analyses were carried out in eight naturally SC-infected and five uninfected sheep with the same genotype for PRNP (ARQ/ARQ). This comparison was performed using real-time RT-PCR in samples of spleen and cerebellum. Results showed differences in the expression of both cytokines in cerebellum (p < 0.05) but not in spleen (p > 0.05).