From the right-hand end of the ectromelia virus (strain Moscow) genome, 32318 bps have been sequenced, and characterized to include a total of 18 open reading frames (ORFs) and six regions which apparently no longer code for functional proteins. At least six of the ORFs appear to be involved in blocking the inflammatory/immune host response to infection, and therefore probably contribute significantly to the virulence of this virus in its natural host, the mouse. One of these genes encoded an isolog of the poxvirus chemokine binding protein, and was shown to be the most abundant protein secreted from ectromelia virus infected cells. Two regions were found to have significant similarity to poxvirus genes encoding tumor necrosis factor (TNF) binding proteins. Both are distinct from cytokine response modifier (crm)B and crmC but only one is predicted to encode a functional TNF binding protein. A novel similarity between the C-terminal domain of poxvirus TNF binding proteins and several other poxvirus proteins is also presented. The results are discussed in the context of ectromelia virus pathogenesis of mice.