Peritoneal exudate macrophages (M phi) of newborn mice (NB-M phi) were apparently almost incapable of expressing Ia antigen even if stimulated by IFN-gamma. No significant difference was observed in the number and the affinity of receptors for IFN-gamma between NB-M phi and M phi of adult mice (Ad-M phi). Addition of indomethacin, a prostaglandin synthesis inhibitor, was ineffective in enhancing the Ia-expression of NB-M phi. Responsiveness of NB-M phi to IFN-gamma, however, was disclosed by the addition to the culture of anti-IFN-beta or anti-IFN-alpha/beta, but not anti-IFN-alpha antibody. Responsiveness of NB-M phi to IFN-gamma was not improved by the depletion of fibroblasts from NB-M phi populations. These results strongly argue that Ia-expression of NB-M phi, which is otherwise to be induced by IFN-gamma, is suppressed by IFN-beta derived from NB-M phi themselves.