Five crystal forms of the amide-type local anesthetic S-bupivacaine hydrochloride (levobupivacaine) were prepared and characterized by means of thermal analytical methods, FTIR-and Raman-spectroscopy, powder X-ray diffractometry, and moisture sorption analysis. Commercial lots of the substance may consist of form A8, the thermodynamically stable form at 208C, and/or the metastable form C. Form A8 shows a highly reversible transformation into form B (T trs : 85.38C) with a transition enthalpy of 4.6 kJ mol ร1 . The hysteresis between the experimental transition temperatures is 3.5 K, indicating a very weak kinetic control. The hydrate shows a variable water content (0.71-1.14 mol/mol) between 10 and 90% relative humidity (RH) and dehydrates to form C under dry conditions or at elevated temperatures. All anhydrous forms transform to the hydrate at and above 90% RH (258C). Form C slowly converts to form A8 on storage and is the polymorph with the highest hygroscopicity. At higher temperatures all forms transform into form D, which is kinetically stable at 208C. It is concluded that the forms A8, B, and D are enantiotropically related, whereas form C shows a monotropic relationship to these forms and is metastable in the entire temperature range.