Thermodynamics and kinetics of serum albumin binding of long-chain fatty acids (FA) with more than 14 carbon atoms are important in all chemical studies of FA in water. Furthermore, the energetics of this process should substantiate the molecular model (Brown, J. R.; Shockley, P. Lipid-Protein Interactions; John Wiley & Sons : New York, 1989; Vol. 1, pp 25-68). At pH 7.3, bovine serum albumin (BSA) has three equivalent high affinity binding-sites for FA to BSA molar ratios below 2 at temperatures between 273 and 311 K. The corresponding Gibbs free energies (Delta G degrees) of six FA transfers from buffer, ionic strength 0.173 M, to BSA are identical with those of transfers to heptane of FA excepting the head groups -CH2-COO- (Smith, R.; Tanford, C. Proc. Natl. Acad. Sci. U.S.A. 1973, 70, 289-293), suggesting similar binding free energy of the anionic head group in buffer and in BSA, corroborating NMR studies (Cistola, D. P.; Small, D. M.; Hamilton, J. A. J. Biol. Chem. 1989, 262, 10980-10985). From Delta H degrees and Delta G degrees of FA transfers from water to BSA and to aliphatic hydrocarbons, we calculate T Delta S degrees and Delta G degrees of the FA hydrocarbon chains transfers from aliphatic hydrocarbons to BSA, with complete entropy/enthalpy compensation (Delta G degrees approximate to 0), The values vary between FA but corroborate known conformational changes of BSA when binding FA. The kinetics of palmitate and oleate bindings reveal transition states of FA with low entropy as in water and higher enthalpies corresponding to carboxyl-group bindings by hydrogen bonds in water. Thus, FA are bound in BSA by combined electrostatic anionic head group bindings and van der Waals bindings of the hydrocarbon tails. The Delta G degrees’s of transfer from buffer are entirely accounted for by transfer of the hydrocarbon tail, making predictable the equilibrium constants of FA-BSA complexes in buffer at pH 7.3.