The HLA class II genes encode heterodimeric cell surface proteins which bind peptide antigen recognized by T-cell receptors on CD4+ T-cells. The class II proteins are inducible by IFN-gamma, and this induction requires, or is strongly enhanced, by retinoblastoma protein (RB) in a series of breast carcinoma cell lines. Loading of peptide onto the class II protein appears to be regulated by CD74, which associates with class II during their transition to the endosomal compartment, where class II binds peptide. Class II proteins and CD74 are largely regulated in concert, provoking the question, is CD74 induction by IFN-gamma affected by RB? Results described here indicate that IFN-gamma induction of CD74 surface expression in a series of breast carcinoma lines is enhanced by RB, while RB has no effect on CD74 mRNA induction. Also, neither the class II nor the CD74 promoter regions are activated by RB in cotransfection experiments where RB activates the SV40 promoter.