Entamoeba histolytica trophozoites were found to be very selective in their interactions with bacteria. Two principal mechanisms were shown to be responsible for these interactions. Certain bacteria, such as a number of Escherichia coli and Serratia marcescens strains which are known to contain mannose-binding components on their cell surface, bound to mannose receptors on the amoeba membrane. This attachment was markedly inhibited by alpha-methylmannoside (0.5%), especially when the incubations were done at low temperature (5 degrees C). Other bacterial species, such as Shigella flexneri and Staphylococcus aureus, which do not possess a mannose-binding capacity, attached to the amoebae, but only with the aid of concanavalin A or after opsonization of the bacteria with immune serum. In both types of attachment, between 40 and 100 bacteria bound per amoeba, and considerable ingestion of bacteria into amoeba vacuoles was observed at 37 degrees C. The attachment of opsonized bacteria to the amoebae does not appear to be mediated by Fc receptors since Fab' dimers obtained after pepsin digestion of immunoglobulin were capable of mediating adherence. Furthermore, preincubation of the amoebae with aggregated human immunoglobulin G or with heat-inactivated immune serum and EDTA did not inhibit the attachment of opsonized bacteria. The attachment of opsonized bacteria was markedly inhibited by N-acetylglucosamine-containing glycoconjugates, such as peptidoglycan and chitin oligosaccharides, as well as by N-acetylgalactosamine. These results indicate that amoebae can attach and ingest bacteria either by using their membrane-associated carbohydrate-binding protein or by having their mannose-containing cell surface components serve as receptors.