The nonspecific biological activity of compounds with cell membranes is of great importance when considering them for pharmaceutical applications. The interactions of a group of therapeutic bispyridinium compounds with phospholipid monolayers of dioleoyl phosphatidylcholine (DOPC) on a mercury electrode (HMDE) are reported in this paper. Impedance versus frequency plots and capacitance-potential curves were recorded for the model membrane system. The penetration of the compounds into the monolayer is shown to be dependent on the applied electric field. Both electron withdrawing and electron donating substituents of the bispyridinium compounds promote interaction with the compounds at applied negative potential.