Recent studies have shown that gamma-interferon (IFN-gamma) induces the expression of Ia antigen on astrocytes. This observation is of immunological significance because such activated astrocytes can act as antigen-presenting cells, as demonstrated with myelin basic protein for antigen-specific encephalitogenic T-cell lines. However, the lack of lymphatic drainage in brain and the presence of the so-called blood-brain barrier restricting traffic of cells and macromolecules suggests that IFN-gamma may not be readily available, at least during the initial phases of viral infections. The question therefore arises as to whether astrocytes can be induced to express Ia antigens by other signals directly related to viral infection and possibly independent of IFN-gamma. In the present report we demonstrate that a neurotropic murine hepatitis virus induces expression of Ia antigen on astrocytes in tissue culture without infection, rendering these brain cells competent to participate directly in the immune response to a viral infection.