Several histidine-tryptophan complexes, derived from the crystal structures available in the Brookhaven Protein Data Bank, have been examined with ab initio theoretical methods (using as model systems 5-methylimidazole and indole, respectively), in order to identify the most favorable arrangements of the two side chains, elucidating also the strength and the nature of the intermolecular interaction established between them. The equilibrium geometries of the isolated partners were optimized at the HF/6-31G* level and the interaction energy of the adducts was computed, employing the 6-31G* basis set with the d exponents reduced to 0.25, thus named 6-31G*(0.25), at the HF and MP2 (frozen-core approximation) levels. For a few typical orientations, the dependence of the interaction energy upon the intermolecular distance, as measured from the ring centroids, was then examined while keeping fixed reciprocal orientations and internal geometries of the partners. There is a fair linear correlation between the equilibrium distances (R-eq) at the MP2 level and the experimental (R-exp) ones and between the MP2 interaction energies at R-eq and those computed at R-exp. For three arrangements with a shallow or even repulsive HF interaction energy, the counterpoise correction to the basis set superposition error (BSSE) was introduced both at the HF and MP2 levels, using Pople＇s 6-31G* standard, 6-31G*(0.25), and Dunning＇s DZP basis sets, to test the reliability of the results obtained along the whole approaching path. This is made necessary by the noticeable displacement in the equilibrium distances usually found at the various levels. The DZP HF interaction energies turn out to be less affected by BSSEs than the 6-31G* and the 6-31G*(0.25) ones and are located in an intermediate position between them. As a general rule for these complexes, the counterpoise correction is larger at the correlated level; therefore the addition of the correlation effect to the counterpoise-corrected SCF energy produces a curve fairly close to the MP2 one that seems to represent a lower bound to the true interaction energy. Kitaura and Morokuma＇s decomposition analysis of the interaction energies was also carried out on these typical complexes.