Protein cation-pi interactions are frequently found near the protein surface with their interacting residues partly solvent exposed. The structurally characterized alpha W-3 model protein contains the W32/K36 cation-pi interaction which has properties similar to those of naturally occurring protein cation-pi interactions. alpha W-3 was studied with the following results: Cation-pi interactions formed by a buried tryptophan and a partly solvated lysine, arginine, or histidine range from -0.8 to -0.5 kcal mol(-1) and rank as: W32/K36 approximate to W32/R36 > W32/H36. The W32/K36 pair in alpha W-3 represents the first W/K cation-pi interaction for which both the structure and the bond energy have been experimentally determined. Upon increasing the solvent exposure of the cation-pi pair, the W/K interaction energy drops from -0.73 to -0.06 and +0.15 kcal mol(-1). These results suggest that solvent exposure can tune the interaction energy between a tryptophan and a lysine by at least 0.9 kcal mol(-1).