We evaluated the role of roIFN-, a type I IFN, as a modulator of blood mononuclear cell (BMC) phenotypes and lung pathology in non-infected, and OvLV-infected lambs. IFN-, the ovine pregnancy recognition signal, has antiviral activity against OvLV and HIV and is less toxic. Similar to HJV, OvLV induces lymphoid interstitial pneumonia. 24 lambs were divided into 4 groups: i) Control; ii) Non-infected+106 antiviral units (AVU) roIFN-/kg/day s.c.; iii) 106 TCID50 OvLV intratracheal + placebo; iv) 106 TCID50 OvLV intratracheal +106 AVU roIFN-/kg/day s.c. BMCs were labeled every week (0-12) with monoclonal antibodies against CD45, CD4, CD8, , MHC II, CD44 and L-selectin (LS) for flow cytometry. The results were compared within (P0.001), and between the groups (P0.01) with the Student-Newman-Keuls test. Individually, roIFN- and OvLV significantly increased the proportions of all the cell markers except MHC II+ cells in the later. OvLV-infected, roIFN--treated lambs showed higher numbers of CD8+, CD4+ and + cells than the non-treated, infected lambs. No significant increase was noticed in the infected, treated group for CD44+ and LS+ cells, Histopathology showed lack of lesions in the lungs of roIFN--treated, OvLV-infected as compared to non-treated, infected group. Enhanced cytotoxic cell numbers and a lack of increase in CD44+ and LS+ cells explain the lack of lung pathology in the roIFN--treated, OvLV-infected lambs.