All living cells, whether in unicellular or multicellular organisms, surround themselves with a shell of carbohydrates. In mammals, epithelial surfaces, which are primarily exposed to other organisms, are particularly rich in carbohydrates. The carbohydrates are characterized by great structural diversity and variability related to individual, species, and cell type. Therefore, carbohydrates are good candidates to be involved in interactions of self with non-self. Microorganisms frequently express carbohydrate binding proteins that may interact specifically with host glycoconjugates (1). Early studies showed that NeuAc, Man, and GM I gangliosides act as receptors for influenza virus, Escherichia coli fimbriae, and cholera toxin, respectively (1). Evidence is now accumulating for the presence of a wide variety of such proteins with many different specificities. Host cell-bacterial interactions can be studied at three levels. At the molecular level, the bacterial binding activities and their specificity are identified and the interacting molecules characterized, i.e., a glycoconjugate on the host and an adhesin or toxin on the bacterium. At the cellular level, binding activities on cultured cells or organ cultures are studied in vitro. At the physiologic level, the biomedical relevance of the binding activities is assessed in animal models and by epidemiologic studies. The article by Dal Nogare in this issue of the journal (2) falls primarily in the latter two categories. Here we will comment on all three approaches, with emphasis on the glycoconjugates of the host. Other mechanisms of host-pathogen interaction are being discovered, such as interaction of bacterial saccharides with host proteins (lectins), protein-protein interactions, hydrophobic interactions, immunologic cross-reactivity between host and microbial antigens, and various other adaptations to the host environment (e.g., 3). However, these are beyond the scope of the present review. The molecular level. In the now classical model of adhesion for gram-negative bacteria, thin appendages (fimbriae, pili) on the bacterial surface interact with glycoconjugates on the host cell surface (1, 4). Improved molecular genetic and biochemical techniques, greater availability of purified complex glycoconjugates, and improved binding assays have now