Three different classes of receptors for the Fc portion of immunoglobulin G (FcRs), FcRI, FcRII, and FcRIII, have been identified on human leukocytes. One of them, FcRI, is a high-affinity receptor capable of induction of functions that include phagocytosis, respiratory burst, antibody-dependent cell-mediated cytotoxicity (ADCC), and secretion of cytokines. This receptor is expressed on mononuclear phagocytes, and this expression is regulated by cytokines and hormones such as gamma interferon (IFN-), IFN-, interleukin-10 (IL-10), and glucocorticoids. We have recently demonstrated that the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is capable of inducing a time-dependent downregulation of both FcRIIIB and FcRII in human neutrophils, altering FcR-dependent functions. Considering the biological relevance of the regulation of FcRI, we investigated the effect of FMLP on the overexpression of FcRI induced by both IFN- and IL-10 on human monocytes. We demonstrate that FMLP significantly abrogated IFN-- and IL-10-induced FcRI expression, although its basal level of expression was not altered. However, other IFN--mediated effects such as the overexpression of the major histocompatibility complex class II antigens and the enhancement of lipopolysaccharide-induced secretion of tumor necrosis factor alpha were not affected by FMLP treatment. The formyl peptide completely inhibited the IFN-- and IL-10-induced enhancement of ADCC and phagocytosis carried out by adherent cells. The inhibitory effect of FMLP on FcRI upregulation could exert an important regulatory effect during the evolution of bacterial infections.