Persistent infection of the central nervous system (CNS) with measles virus (MV) is associated with characteristic restrictions of viral envelope gene expression as documented in subacute sclerosing panencephalitis (SSPE), measles inclusion body encephalitis (MIBE), or subacute measles encephalitis (SAME) in rats. To determine whether these restrictions are the result of a long lasting virus-host cell interaction or primarily based on intrinsic brain cell factors MV gene expression was analyzed in primary rat astroglial cultures. It could be shown that MV infection of these cells led to a defective replication cycle with a reduced synthesis of viral envelope proteins and a steep expression gradient of the monocistronic viral mRNAs similar to the findings in brain tissue of SSPE, MIBE, and SAME. This restriction of MV gene expression has not been observed in cells of nonneural origin. We suggest that this cell-type specific regulation of MV gene expression contributes to early events in the establishment of MV persistent infection in CNS tissue.