AbstractTumor necrosis factor‐α (TNFα) induces surface expression of class II major histocompatibility (MHC) molecules (la molecules) in many cells, including macrophage‐like cell lines. When we tested the effects of this cytokine on murine peritoneal macrophages, TNFα had little effect on surface expression of la. The strong expression of such molecules induced by interferon‐γ (IFN‐γ) was, however, suppressed moderately by TNFα. These effects were reflected at the level of specific messenger RNA (mRNA) as detected by Northern blot analysis. Furthermore, the locus of control appears to be transcriptional; in nuclear run‐on assays, TNFα suppressed the IFNγ‐induced enhancement of transcription for the murine β‐chain of l‐A (l‐Aβ.). Taken together the data suggest that TNFα has little effect on class II MHC genes and surface expression in murine peritoneal macrophages, that TNFα is a modest suppressant of such molecules when their levels are raised by IFNγ, and that these suppressive effects are mediated at the level of transcription.