Contacts between aromatic and charged residues are often found in proteins. Mutational studies have shown that a tryptophan/charged histidine pair can stabilise a protein by more than 1 kcal mol(-1). We have used circular dichroism and nuclear magnetic resonance to study the helical content of several peptides in which a tryptophan/histidine pair was placed at i, i + 3 or i, i + 4 in either the N to C or the C to N orientation. Our data indicate that the WH i, i + 4 geometry is the most stabilising one (when the histidine is protonated) and gives rise to the highest helical content. Little preference is observed among the three other orientations. The energy of the WH+ i, i + 4 interaction (calculated with AGADIR and SCINT) is about 1 kcal mol(-1). A statistical analysis of the occurrence of tryptophan/histidine pairs in alpha-helices of natural proteins reveals that, although the WH i, i + 4 pairs are not more abundant than the others, in most of the WH i, i + 4 pairs the two side-chains are in contact, but not in the other three orientations. These results suggest that the conformational stability of proteins could be increased by means of solvent-exposed intrahelical i, i + 4 tryptophan-histidine bridges and that these bridges could be useful to tailor the stability of helical peptides at physiological pH.