High-pressure Raman spectroscopy has been used to study tris(hydroxymethyl)aminomethane (C(CH2OH)(3)NH2, Tris). Molecules with globular shapes such as Tris have been studied thoroughly as a function of temperature and are of fundamental interest because of the presence of thermal transitions from orientational order to disorder. In contrast, relatively little is known about their high-pressure behavior. Diamond anvil cell techniques were used to generate pressures in Tris samples up to similar to 10 GPa. A phase transition was observed at a pressure of similar to 2 GPa that exhibited relatively slow kinetics and considerable hysteresis, indicative of a first-order transition. The Raman spectrum becomes significantly more complex in the high-pressure phase, indicating increased correlation splitting and significant enhancement in the intensity of some weak, low-pressure phase Raman-active modes.