We established cultures of human astrocytes and astrocytoma cells from surgical specimens, to study regulation of class II major histocompatibility (MHC) complex antigen expression by interferons. Using these cultures we previously showed that expression of the class II MHC determinant HLA-DR could be induced by interferon-gamma and this induction was inhibited by interferon-beta. In this report, we extend these observations by showing that the inhibitory effect of interferon-beta on interferon-gamma induction of the class II MHC gene HLA-DR alpha was exerted at the transcriptional level, as documented by nuclear run-on experiments and confirmed with blot hybridization analysis. Astrocyte expression of intercellular adhesion molecule-1 (ICAM-1) was induced efficiently by interferon-gamma, but not by interferon-beta, and induction of ICAM-1 expression by interferon-gamma could not be impaired by interferon-beta, suggesting that the suppressive effect on induction of HLA-DR was relatively gene-specific. Furthermore, interferon-beta did not antagonize interferon-gamma induction of HLA-DR expression in human monocytes, suggesting that the inhibition observed in astrocytes was relatively tissue-specific.