The phase diagram for the binary system nafcillin sodium-water, was determined using differential scanning calorimetry (DSC) and polarized light microscopy. In the temperature range of -20-30 degrees, three crystalline forms and an amphiphilic liquid crystalline phase were detected. The stable crystalline form of nafcillin sodium (form alpha) and water exhibit a eutectic mixture containing 28% drug (w/w) at -1 degrees. In more dilute solutions a lower temperature eutectic (-5 degrees) occurs. The composition and form of nafcillin sodium in this eutectic are not known. The form -5 degrees eutectic was found to be metastable above 28% concentration and converted to form alpha. Two other crystalline forms were observed at 9 degrees (form beta) and 22 degrees (form gamma) at concentrations above 40%. The crystalline forms could not be further characterized due to their transient nature and existence in highly concentrated mixtures. A lamellar mesophase is present near ambient temperature in mixtures containing more than 55% nafcillin sodium. The phase equilibria were highly susceptible to supercooling. Temperature cycling methods were devised which gave reproducible DSC data and allowed construction of the phase diagram.