Based on the differential susceptibility to infectious diseases between and within breeds and on the recent findings regarding the putative involvement of TLR9 in disease susceptibility, the aim of this study was to evaluate the levels of nucleotide variation of TLR9 and its mediator MyD88 in three sheep flocks originated from different breeds and assess their possible association with seropositivity/seronegativity for different infectious agents. The gene discussed is TLR9; the disease is infectious disease.