Surface potential (delta V) measurements were performed to assess information on insulin penetration/interaction with dipalmitoylphosphatidylcholine (DPPC) monolayers spread at the water-air interface. The results reveal existence of the threshold surface density value of spread lipid molecules (7.5 x 10(13) molecules/cm2) above which none penetration of insulin molecules occurs. Surface potential data clearly indicate also that insulin penetration/interaction with DPPC monolayers is enhanced in the presence of the second studied constituent of these monolayers in the order DPPC + stearylamine greater than DPPC + cholesteryl betainate greater than DPPC + cholesterol greater than DPPC. The results clearly indicate the existence of two types of phospholipid-insulin interactions namely: adsorption and penetration.