In order to target liposomes to cells expressing at their surface mannose receptors (MR), alkylmannosides differing in length of the hydrophilic spacer between sugar head group and lipid backbone - from 0 through 8 ethylene glycol units (Man0...Man8) - were incorporated into liposomes. Gradual prolongation of the spacer should investigate recognition by receptor proteins systematically. Interaction of liposomes with phagocytes representing the MR (human peritoneal and pericardial macrophages) and macrophage-like cells lacking the MR (differentiated HL60 and U937 cells) was studied. Detection of MR was carried out by testing of receptor function and a monoclonal antibody assay. Liposomes containing mannosides with more than one ethylene glycol unit (EtO) spacer length were specifically aggregated by ConcanavalinA (ConA), indicating that the surface ligands were accessible to the lectin. Uptake of liposomes containing mannosides with short spacer arms (0 or 1 EtO) by cells both expressing and lacking the MR was enhanced, due to improved adherence of the liposomes. For binding to receptor proteins, if at all, concentrations of up to 40 mol% of these derivatives were necessary. Taking destabilization of the liposome membrane by high amounts of glycolipids into account, short spacer mannosides are not suitable as targeting devices. In contrast, mannosides with longer spacer arms (more than 2 EtO) are able to bind to receptor proteins at lower molar concentrations. Liposome uptake by MR expressing native macrophages was improved particularly by Man6 and Man8. Most effective binding by ConA was detected using Man6, while interaction with MR of native cells did not reach an optimum in dependence on the spacer length. Thus, besides Man6 and Man8, derivatives with longer spacer arms seem to be attractive tools to reach receptor mediated targeting. Liposome uptake by cells lacking the MR was suppressed by incorporation of longer mannosides (spacer >= 2 EtO). Extent of suppression increased with spacer length and was independent on sugar head group: similar results were obtained using glucosides, galactosides and cellobiosides of identical structure, indicating a barrier function of these longer derivatives similar to Stealth® lipids. Furthermore it could be shown, that not only the distance between sugar head group and liposome membrane but also the spacial organization of the ligands is of decisive importance for protein recognition. Although a minimum length of the spacer is necessary, the spacer length mainly influences the tendency of phase separation and clustering of the mannosides. Moreover spacer length determines flexibility of the distinct carbohydrate ligands. Thus, an approptiate spatial arrangement of the ligands, dependent on clustering and flexibility, is necessary to reach effective binding by receptor proteins. The use of relatively simple compounds, as the glycolipids tested here, variing in spacer length, molar concentration and lipid composition of the liposomes, represents a flexible system to investigate the complex mechanisms, which take part in carbohydrate protein recognition as a tool for receptor mediated targeting.