The interaction of theophylline with L-tryptophan was investigated in aqueous solution adjusted to ionic strength 0.20, at pD 6.2, by using proton nuclear magnetic resonance spectroscopy. Theophylline interacted with L-tryptophan at a molar ratio of 1 : 1 by parallel stacking. The thermodynamic parameters obtained for the complexation were as follows : ΔG°=-1.52kcal/mol (K=13.1M-1), ΔH°=-5.1kcal/mol, ΔS°=-12.3 e.u. It was found that the driving force for parallel stacking is a combination of electrostatic, polarization, and dispersion interactions, and the contribution of hydrophobic bonding is small. A possible stacking mode is postulated, based on the complexation shifts and π-electron charge distributions of theophylline and L-tryptophan.