Interleukin 10 (IL-10) is a pleiotropic cytokine that plays an important role in regulating inflammatory and immune responses. It is a potent suppressant of proinflammatory cytokine production by monocytes/macrophages and neutrophils. It is also an inhibitor of macrophage and T cell effector functions. Homologs of mammalian IL-10 have been identified in the genome of several viruses, including Epstein-Barr virus (EBV), poxvirus Orf, baboon cytomegalovirus, and human and equine herpes virus. In the EBV genome, the BCRF1 open reading frame encodes the EBV IL-10 (vIL-10). The viral IL-10 precursor is a 170 amino acid residue (aa) protein with a putative 25 aa signal peptide that is cleaved to yield the 145 aa mature protein. The EBV IL-10 precursor shares approximately 78% and 65% amino acid sequence homology with human and mouse IL-10, respectively. Most of the deviations are localized to the signal peptide and the first 20 amino-terminal residues. Viral IL-10 is expressed during the late phase of the lytic cycle of EBV infection. Viral IL-10 is a partial agonist of mammalian IL-10 and shares many of their activities. It is likely that vIL-10 may have a role in host immune evasion.