H-2 class I antigens, but not class II antigens, were detected on the surface of glial cells persistently infected with mouse hepatitis virus strain A59 (MHV-A59) as late as 90 days post-infection. Uninfected glial cells remained negative for H-2 class I and class II surface antigens. We have previously shown that conditioned media from infected glial cell cultures (supernatants) contain a factor unrelated to infectious virus and capable of inducing H-2 class I antigens on uninfected glial cells. The synthesis of this factor appears to be dependent on production of infectious virus since the H-2 inducing activity could not be detected 3 days following the addition of neutralizing antibodies to the cultures. This suggests that H-2 inducing activity contains an unstable component, the synthesis of which is dependent on continual virus production. Persistent MHV infection and H-2 class I antigen expression may play a role in MHV-induced demyelination.