The interaction of 12 antisense nucleosides with phenylalanine (Phe), and the effect of pH and salts on the strength of interaction was studied by charge-transfer reversed-phase thin-layer chromatography. Phe significantly decreased the lipophilicity of nucleosides. This effect may be due to the interaction between the more hydrophilic Phe and the more lipophilic nucleosides, resulting in charge-transfer complexes of moderate lipophilicity. The relative strength of interaction was the weakest in acidic and the strongest in alkaline environment. This finding indicates the partially or entirely hydrophilic character of the interaction. Salts influenced to a lesser extent the interaction, their effect depended both on the concentration and on the type of cation. The relatively low impact of salts on the strength of interaction suggests that other than hydrophilic forces are involved in the Phe - antisense nucleoside interaction.