Phase equilibrium behavior of antibiotics is important in drug design and for optimization of the recovery processes in manufacturing. Antibiotics are high-cost fine chemicals, mostly manufactured by fermentation using inexpensive substrates. The major cost of manufacturing is involved in the separation processes. The aqueous/organic partitioning behavior of a clinically important antibiotic, chloramphenicol, is measured. The organic phase includes the pure solvents n-hexane, chloroform, diethyl ether, and ethylacetate. In addition, measurements are also made for a mixed organic phase composed of n-hexane + ethyl acetate. Partitioning increases with the hydrogen bonding tendency of the solvent in the order n-hexane < chloroform < diethyl ether < ethyl acetate. Based on UNIQUAC and lattice-fluid hydrogen-bonding theories, an activity coefficient model (UNIQUAC-HB) is developed that includes hydrogen-bonding interaction. Single-solvent organic-phase data are correlated with the model, and free energy of hydrogen bonding parameters are obtained. Predictions made for mixed-solvent organic-phase systems agree well with the experimental data without using any adjustable parameter.