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Background: Several di-substituted 2-hydroxyacetamides have shown promising antimycobacterial activity. In an attempt for further development of these compounds which are easily synthesized, investigation of the relationship between their physicochemical properties and inhibitory activities appeared of interest. Since lipophilicity as a physicochemical parameter plays an important role on biological activity and drug design, the relationship between partition coefficient as a measure of lipophilicity and antimycobacterial activity of the studied compounds was investigated. Methods: Partition coefficients of 2-hydroxyacetamides a-n measured by the shake flask (log P), reversed-phase high-performance liquid chromatography (RP-HPLC log κ) methods and by theoretical calculation (ClogP) were compared and the relationship between the resulting values and antimycobacterial activities of the studied compounds determined by Alamar Blue Assay was investigated. Results: When all compounds were included in the correlation analyses, no significant relationship between MICs (minimum inhibitory concentrations) and lipophilicity parameters was observed, but HPLC values showed significant correlation with ClogP. The best correlation between MICs and lipophilicity parameters for di-substituted amides g-n which were more active than mono-substituted amides were RP-HPLC based log κ and for mono-substituted amides were shake flask log P values which in both cases were not significant. When deviating compounds m and n were excluded from the correlation analyses, for di-substituted amides, correlation between MICs and log κ as well as correlation between values of partition coefficient by different methods became significant. Conclusion: Results of this investigation indicates that both ClogP and log κ are equally suitable for prediction of partition coefficient. [ABSTRACT FROM AUTHOR]