In this study the interactions between erythromycin and various polymers (Eudragit L100, shellac, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose acetate phthalate (HPMCP), and hydroxypropyl methylcellulose (HPMC)) were investigated. The polymer films containing drugs were prepared and characterized by the use of infrared spectroscopy, powder X-ray diffraction analysis, thermal analysis, thin layer chromatography, and nuclear magnetic resonance (NMR) spectroscopy. Preliminary studies of pure drug powders recrystallized in various organic solvent systems suggested a mixture of amorphous and crystalline forms whereas those recrystallized in water and organic solvent-water mixture led to the dihydrate form. Erythromycin in drug-polymer mixtures exhibited molecular dispersions in all six polymers studied. The amine salt interaction between the carboxyl group of the acid polymers and N-atom of erythromycin was indicated by the NMR technique. The solid solution of erythromycin in all polymer films studied was physically stable under stress conditions (8 degrees C/3 days and 40 degrees C/3 days for six cycles).