Many recent reports have discussed specific effects of anions on the properties of lipid membranes and possible roles of such effects within biochemistry. One key parameter in both theoretical and experimental treatments of membrane-salt interactions is the net affinity, that is, the free energy of interaction. This parameter has been analyzed theoretically and by modeling of experimental data but not directly measured even for simple salt-membrane systems. To provide such information, we have studied the interaction of unilamellar liposomes of dimyristoyl phosphatidylcholine (DMPC) and eight sodium salts by dialysis equilibrium measurements. This method provides model free thermodynamic data and allows investigations in the dilute concentration range where solution nonideality and perturbation of membrane structure is limited. The transfer free energy of DMPC from water to salt solutions, Delta mu(2,trans), was found to scale proportionally to the salt concentration, m(3), in the 0-50 mmolal range, and we suggest that the slope, Delta mu(2,trans)/(out)m(3), represents an experimental salt-membrane interaction potential. The values of Delta mu(2,trans)/(out)m(3) for sodium salts of monovalent anions ranged from +2.2 kJ (mol.molal)(-1) for F(-) to -16.9 kJ (mol.molal)(-1) for SCN(-), thus confirming a distinct membrane specificity among the anions. For Na(2)SO(4), the interaction was strongly unfavorable with Delta mu(2,trans)/(out)m(3) = +20.6 kJ (mol.molal)(-1). The dialysis data were supplemented with calorimetric measurements and analyzed with respect to a two-domain model.