The solution conformations and dynamics of the antidepressant drug trimipramine maleate were investigated by 'H and I3C NMR spectroscopy. Of particular interest was an observed non-equivalence of the N-methyl groups in the aliphatic sidechain of the drug, which is present in both 'H and I3C spectra under a range of aqueous and non-aqueous solvent conditions when the terminal nitrogen is protonated. Although the inequivalence was first observed for the maleate salt, the nature of the counter ion is not a determining factor. The solution concentration of the drug does, however, modulate the observed inequivalence, with the two peaks coalescing at higher drug concentrations. The diastereotopic environments of the two methyl groups arise because of a chiral centre in the aliphatic side-chain. Inversion of the terminal nitrogen produces exchange between the two environments, thereby destroying the inequivalence and leading to a single averaged resonance for the two methyl groups. The energy barrier for the exchange process was determined from variable-temperature NMR experiments to be 16.3 kcal ml-I (1 kcal = 4.184 kJ). This is higher than would be expected for simple inversion of a tertiary nitrogen, but reflects the fact that inversion can only occur for the small fraction of molecules which are not protonated. The barrier determined from the variable-temperature experiments was in agreement with rates of interchange between the two methyl environments determined from saturation transfer experiments. These rates were measured for a series of different protonation states of the nitrogen, with the rate contant for interchange of environments decreasing with an increasing degree of nitrogen protonation. "C spin-lattice relaxation times and nuclear Overhauser enhancement effects were also measured to determine the degree of mobility in the aliphatic side-chain of trimipramine maleate.