A method is described to control nucleation and coarsening in the process of protein crystallization. The control of these events is achieved by combining a biphasic oil/water system with a multi-compartment crystallization device. The addition of oil resulted in a significant decrease of the diffusion rate of a precipitant agent solution. When compared with crystal growth in the absence of oil, significantly smaller amounts of initially precipitated protein were observed. Thus, this method shifts crystal growth from a nucleation-coarsening (Ostwald ripening) equilibrium to a new equilibrium where Ostwald ripening is drastically diminished. Moreover, larger, rod-shape, high quality single crystals can also be obtained as a result of this equilibrium shift. (C) 2003 Elsevier Science B.V. All rights reserved.