Phospholipid monolayers adsorbed at the air-water interface are useful model membranes and have been employed to study the interactions between phospholipids and blood clotting factors I and VII. Factor I is a non-membrane-binding protein and was found to penetrate both distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidylcholine (DPPC) monolayers at low lipid pressures. At high lipid pressures, the protein was crowded out of the interface. Factor I penetration of phospholipid monolayers was independent of hydrocarbon chain length, while penetration was maximized with electrolytes in the subphase, Factor VII is a membrane binding protein and was found to penetrate a DPPC monolayer only when electrolytes were added to the subphase, Factor VII penetrated DSPC monolayers regardless of electrolyte addition in the subphase, and its interactions with DSPC films are attributed to protein-lipid hydrophobic interactions,