Mixed monolayers were prepared using phospholipids in order to mimic cell membranes and fractions of capsaicinoids (extracted from Malagueta, Caps-M, and Bhut Jolokia, Caps-B, peppers). According to their surface-pressure isotherms and polarization-modulated infrared reflection absorption spectra (PM-IRRAS), weak molecular-level interactions were observed between Caps and phospholipids. Both Caps-M and Caps-B penetrated into the alkyl tail region of the monolayer, interacted with the phosphate group of the phospholipids and affected hydration of their C=O groups. Since the physiological activity of Caps is not governed solely by interaction with cell membranes, it should require participation of a neuronal membrane receptor, e.g. vanilloid receptor (TRPV1). (C)2017 Elsevier B.V. All rights reserved.