Human monocytes isolated from peripheral blood phagocytized polystyrene particles, Escherichia coli, Staphylococcus aureus, Candida albicans, Cryptococcus neoformans, and red cells coated with IgG antibody in vitro. The ingestion of fungi and bacteria required serum or serum fractions. Ingestion of antibody-coated erythrocytes was inhibited by whole serum or IgG, but not by IgM or albumin. Adherence to a surface appeared to be critical for erythrophagocytosis but not for ingestion of bacteria. Phagocytosis occurred over a broad pH range and in the presence of inhibitors of oxidative metabolism and of RNA synthesis. Phagocytosis was significantly depressed by inhibitors of glycolysis (iodoacetate and fluoride) and by chloroquine at 1 x 10-5M. Particle ingestion by monocytes was accompanied by enhanced production of C14O2 from glucose-1-C14, but was not associated with a detectable increase in total glucose utilization, incorporation of radioactive uridine into RNA, or incorporation of amino acids into protein.