MHC class II molecules are expressed in a limited number of cell types, including B lymphocytes and macrophages (Mφ). IFN-γ increases the surface expression of class II molecules in a murine B cell line without inducing detectable changes in either IA or IA mRNA levels. In bone marrow-derived Mφ, IFN-γ causes an increase in class II expression at both the mRNA and surface levels. In addition to the increase in transcription rates described for Mφ, IFN-γ increases the rate of synthesis of IAα and IAβ proteins and the ribosome loading for both mRNA molecules in both cell types. Interestingly, there is a significant peak of free IA mRNA in noninduced cells. Therefore, IFN-γ regulates the expression of MHC class II molecules at the translational level in both B cells and Mφ and, as already reported, at the transcriptional level only in Mφ. The actual mechanism of regulation causes changes in the translation initiation rates in both cell types, as demonstrated by an increase in ribosome loading in polysome gradients.