Nonspecific colloidal forces play an important role in controlling the adhesion of cells and liposomes to surfaces, A better understanding of cell-surface interactions is therefore needed for the development of improved drug delivery systems and biomemetic materials, The nonspecific interactions between model cells and a glass plate at low ionic strengths were quantified using total internal reflection microscopy (TIRM). Model cells were developed using 4.32 and 9.98 mu m polystyrene spheres coated with phospholipids. Varying ratios of zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and negatively charged dimyristoyl phosphatidylglycerol (DMPG) were used to coat the spheres to mimic the lipid charge composition of actual cell membranes, Measured potential energies of interaction between the model cells and a glass plate show excellent agreement with theoretical predictions based on an exponential model for the electrostatic energy. Debye lengths calculated from the experiments agree well with those predicted from solution conductivity measurements, The data presented show that TIRM is very effective in measuring interaction forces in model biological systems and can be used to screen potential stabilizing molecules for use in liposomes and biomimetic materials.