The role of endogenously produced interferon alpha/beta in the functional maturation of newly derived mononuclear phagocytes was investigated. Addition of highly specific anti-interferon alpha + beta antiserum to murine marrow cultures stimulated with colony-stimulating factor-1 (macrophage growth factor) markedly suppressed the capacity of resulting progeny mononuclear phagocytes to ingest opsonized sheep erythrocytes (EAIgG). This impairment was corrected either by direct addition of interferon alpha + beta at a concentration in excess of that neutralized by the antiserum or by the addition of lesser amounts of interferon (33 U/ml) following removal of the anti-interferon from the cultures. Conditioned media from control colony-stimulating factor-stimulated cultures similarly reversed the impairment of maturation resulting from 5 days of growth in the presence of anti-interferon. This enhancement of EAIgG ingestion reflected upon the interferon activity in the conditioned media and was neutralized by anti-interferon. Lastly, the endogenous interferon was found to enhance EAIgG ingestion by a majority of the mononuclear phagocyte progeny and not by a limited subpopulation.