IR studies were performed to determine the interaction of caffeine and sulfamethoxazole (SMX). The observed changes in spectral position and shape of characteristic IR bands of caffeine and SMX in the IR spectrum of interacted compound were compared with those of free caffeine. and SNIX molecules. Investigations of the infrared spectrum of interacted compound indicated that the vibration due to the NH stretching of sulfonamido, group is shifted toward a lower wave-number when compared with free SMX molecule. To explain the observed changes in IR spectrum of interacted compound upon interaction between caffeine and SMX molecules semi-empirical PM3 calculations on the samples have also been carried out. The results showed that SMX do not complex with caffeine strongly and the weak hydrogen bonding interaction between imidazole ring of caffeine and sulfonamido group of SMX The X-ray diffraction studies also showed that there is an interaction between caffeine and SMX molecules. (C) 2002 Elsevier Science B.V. All rights reserved.