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We investigate electric potential differences across lipid mono- and bilayers. Apart from externally applied electric fields, these differences are created by two sources: either by ions (dissociation of ionic groups or accumulation at the lipid layer) or by a net orientation of dipoles. The first leads to so-called surface potentials and is fairly described by the Gouy-Chapman theory. The second yields to the dipole potentials and a complete theoretical model is still lacking. Both sources change the electric potential in the lipid moiety. This internal electric potential provides a selective barrier for ion transport across membranes, and its control is the primary target of many drugs. Moreover, changes in the electric transmembrane gradient modify the elastic properties of a membrane and eventually even may induce shape transitions of liposomes or cells. We injected various concentrations of three different types of molecules either into the subphase below a lipid monolayer or into the phases adjacent to a planar lipid bilayer and recorded the successive change in electrical transmembrane potential difference. The first molecule was polyethylene glycol (PEG) which is supposed to modify the water structure at high concentrations. The second was Dibucaine, a local anesthetic, which has a high affinity, being accommodated between the lipid headgroups and the lipid tails. The third substance was Salmeterol, a bronchodilator, which has a higher affinity to the lipid phase than Dibucaine but the localization inside the lipid membrane is not known. The different action of the substances on mono- and bilayer potentials is discussed. [ABSTRACT FROM AUTHOR]