The lipophilicity of zwitterionic amino acids was determined by measuring their distribution coefficients in an octan-1-ol-buffer system at pH values near their isoelectric point (log D(i)) using centrifugal partition chromatography (CPC). The observed differences in the lipophilic expression of methylene groups in the side-chain of alpha-amino acids are interpreted as a consequence of their different electronic structure and/or hydration features due to proximity effects exerted by the dipolar +H3N-CH-CO2- moiety. A comparison of non-additive log D(i) increments of methylene groups in a flexible alkyl and relatively rigid cycloalkyl side-chain of alpha-amino acids leads to the conclusion that the flexible alkyl side-chain is not fully accessible to solvents. The influence of intercharge distance on lipophilicity was examined with homologous piperidinyl carboxylic acids, indicating a decrease 0.4 log D(I) units per increase of 1 angstrom between opposite charges. Among flexible non-alpha-amino acids, an increase in lipophilicity increment is observed only when the seventh carbon is added between the two opposite charges. As for the lipophilicity of N-alkylated zwitterions, N,N-dimethylglycine is shown to be less lipophilic than N-methylglycine, a finding of potential interest in the context of metabolic reactions of N-dealkylation. It is postulated that amino acids are transferred into lipidic phases in the form of hydrates, implying that the latter may have biological significance