The partition coefficients of several 1,4-benzodiazepin-2-ones (BZDs) were determined in a synaptosomal membrane-buffer system (Pm/b) by a two-component model analysis of the experimental data and the following values were obtained: flunitrazepam (FNTZ) = 32.2 +/- 1.5; diazepam (DZ) = 79 +/- 9; clonazepam (CNZ) = 30 +/- 4; nitrazepam (NTZ) = 38 +/- 2 and chlorodiazepoxide (CDZX) = 15.7 +/- 0.6. Correlations between these Pm/b and other chemical properties were performed by a principal component analysis. Hydrophobicity of BZDs, measured as the partition coefficients in different solvent systems, could be correlated with the presence of a methyl group at position 1 of the seven-member ring of the BZD molecule. The values of the partition coefficients of benzodiazepine in the synaptosomal membrane-buffer system were one order of magnitude lower than those obtained in an octanol-water or in ethyl acetate-water systems. The complexity of the membrane, unlike the isotropy of a pure solvent phase, provides a wide spectrum of types of interactions which, in turn, can be modulated in a dynamic manner by local or generalized changes in the lipid phase state. In that sense, the present values of Pm/b should be interpreted as an average tendency of BZDs to establish non-specific interactions with the molecules present in the different phases within biological membranes. Conversely, these Pm/b values reflect a consequence of the difference in complexity between natural membranes and the systems currently used as membrane models for drug partitioning.