The miscibility, mechanical and morphological properties of mixed Langmuir and Langmuir-Blodgett monolayers prepared from the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and the perfluorinated fatty acid perfluorooctadecanoic acid have been studied as a function of film composition and subphase salinity. It was demonstrated here, for the first time, that the extent of surfactant miscibility in mixed phospholipid-perfluoroacid monolayers, and hence the resulting mechanical properties of the monolayer film, can be controlled by altering the concentration of sodium ions in the underlying subphase. Elevated Na+ concentrations resulted in lower net attractive interactions between film components, likely through specific ion adsorption to the negatively-charged perfluoroacid, along with decreased film elasticities. These results differ significantly from conventional fatty-acid - carboxylate monolayer systems in which film cohesion is typically enhanced through adsorption of cations to surfactant headgroups. Atomic force microscope images of films deposited onto solid mica substrates revealed that the films deposited from pure water formed multimolecular aggregates of surfactant, which could be attributed to the highly cohesive nature of the films, but the use of salt in the subphase diminished aggregate formation and resulted in the production of homogeneous monolayer films. Crown Copyright (c) 2010 Published by Elsevier Inc. All rights reserved.