A quantitative structure-retention and retention-activity relationships investigations were performed on the lipophilicities of some 1,3-oxazolidine systems as estimated by RP-HPTLC retention parameters. The classical R(Mo) values were compared with the factors scores obtained by principal component analysis based also onto the TLC retention data. The lipophilicities (R(Mo) and factor scores) were correlated with the theoretical molecular descriptors of 1,3-oxazolidine derivatives providing by the ALCHEMY 2000 software package. The reliability of the factor scores values as lipophilic indices are shown by their significant correlation with the classical R(Mo) values and other molecular descriptors. In addition, the "lipophilicity chart" described by the first two components, and/or the "lipophilicity space" described by the first three components have the effect of separating compounds from each other most effectively from the congeneric (similarity) aspect point of view. Finally, these findings support the idea that the chromatographic process of the investigated compounds in this paper and consequently their partitioning over a bio-membrane are controlled mainly by lipophilicity.