The aim of this work was to study the interaction of pirarubicin, an anthracycline used in chemotherapy, with planar palmitoyloleoylphosphatidylcholine (POPC) monolayers and bilayers employed as membrane models. Different modes of preparation were used and compared, after a preliminary surface pressure study had been done to determine the characteristics of the pirarubicin-POPC interaction and the level of pirarubicin incorporated in phospholipids. A first method consisted of studying the adsorption of the antibiotic (in aqueous solution) in a POPC monolayer kept at a constant pressure. The final monolayer was composed of almost 11% of pirarubicin in the POPC/pirarubicin mixture at 25 mN/m. The second method consisted of spreading mixtures of POPC/pirarubicin (pirarubicin being now dissolved in an organic solvent) at the air-water interface : the maximum percentage of pirarubicin in the monolayer was 38% at 25 mN/m. These two kinds of monolayers were then transferred by a Langmuir-Blodgett technique onto prisms previously coated with silver. Surface-enhanced resonance Raman spectroscopy gave information about the orientation of the molecules with respect to the silver coating. These spectra were compared with those of pure POPC bilayers transferred onto the prism and then put in contact with an aqueous solution of pirarubicin. Different results were observed for the orientation of pirarubicin in the bilayers (tilted or parallel to the silver), according to the mode of preparation of the samples, underlining the importance of the choice of the experimental protocol and precautions to take in the examination of the results.