Fluorescence quenching was used to determine the distribution coefficient K _d for a tuberculostatic rifabutin in a liposome-water system at pH 6.4 and 7.4. Liposomes were large unilamellar vesicles composed of phosphatidylcholine or its mixtures with cholesterol or cardiolipin and containing a fluorescent label (anthryl phosphatidylcholine with the fluorophore in the hydrophobic region). The K _d values calculated in the Stern-Volmer model are comparable for phosphatidylcholine and phosphatidylcholine/cholesterol at both pH, and testify to rifabutin hydrophobicity (logK _d ≈ 2.4–2.6). Inclusion of negatively charged cardiolipin increases the K _d by more than an order of magnitude at pH 6.4, and ionization of the second phosphate at pH 7.4 produces an additional increase. These results demonstrate the large contribution of electrostatic forces into the interaction of rifabutin with model membranes.