The colloidal stability of cationic 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) liposomes was measured in the presence of guar, carboxymethyl guar, hydroxypropyl guar (HPG), and in mixtures of HPG with boric acid. Carboxymethyl guar induced DOTAP aggregation, presumably by bridging flocculation. The interaction with HPG-borate, an anionic polyelectrolyte with labile charge groups, depended on ionic strength. Without added salt, HPG-borate (pH 9.2) adsorbed on the liposomes and destabilized them. In contrast, in 0.1 M NaCl, HPG-borate did not adsorb onto the liposomes. HPG, HPG-borate, and guar induced depletion flocculation of the liposomes at high polymer concentration. Depletion flocculation may be an important mechanism when HPG is employed in artificial tear formulations.