Poxviruses encode a variety of immunomodulatory proteins that subvert the cytokine networks of infected hosts. Myxoma virus, a poxvirus pathogen of rabbits, expresses two distinct 35‐ to 40‐kDa secreted glycoproteins that bind a broad spectrum of chemokines. The first of these, designated M‐T7, is encoded by the T7 gene and is the first example of what is here referred to as type‐I chemokine binding protein (CBP‐I). M‐T7 was initially discovered as a secreted viral homologue of cellular interferon‐γ receptor but binding studies indicate that purified M‐T7 protein also interacts with members of the CXC, CC, and C chemokine families through the conserved heparin‐binding domains. The second myxoma protein, M‐T1, also called CBP‐II, is a member of a larger superfamily of poxvirus proteins that includes related secreted 35‐kDa proteins encoded by a wide variety of orthopoxviruses. Deletion analysis of either CBP‐I or ‐II genes within recombinant poxvirus constructs revealed profound alterations in the trafficking of infiltrating leukocytes into virus‐infected lesions. It is proposed that the interaction of CBP‐I with the conserved heparin‐binding domains found on most chemokines represents a novel mechanism for altering multiple chemokine functions in vivo. In summary, CBP‐I and CBP‐II are the first examples of secreted virus proteins that bind to multiple chemokine family members as part of a strategy to prevent the early phase of inflammatory cell migration into virus‐infected tissues. J. Leukoc. Biol.62: 570–576; 1997.