For a virus to cause persistent infection in a host, a unique host–virus relationship is required. The virus per se, or variant(s) arising in vivo, must be noncytopathic for the host cell that it infects. Furthermore, the infected cell must escape recognition by the host's immune system, which eliminates virus and virus-infected cells. Several models of persistent infection in vitro demonstrate selective loss of viral gene products normally represented at the cell surface as opposed to viral products found inside the cell1–5. Decreased glycoprotein (gp) expression on the surface of an infected cell correlates directly with the ability of that cell to resist killing by both cytotoxic lymphocytes and cytotoxic antibody and complement1,3,6. The question remains of whether a corresponding selective loss of viral glycoprotein expression occurs in persistently infected cells in vivo. We have used monoclonal antibodies as probes to define the viral glycoprotein and nucleoprotein (NP) molecules expressed in individual cells from several tissues of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). We report here a selective decrease in the expression of viral glycoprotein in single cells, during persistent infection in vivo.