Efficient enzyme-catalyzed syntheses may be carried out even when most of the starting materials and products are in the form of suspended solids. To some examples in the literature of such solid-to-solid conversions, we add the thermolysin-catalyzed reaction of X-Phe-OH (X = For, Ac, Z) with Leu-NH2 to give X-Phe-Leu-NH2. This can proceed to equilibrium yields of over 90% even in aqueous media. Thermodynamic analysis of such systems shows that solid-to-solid conversion itself will be equally favorable in any solvent at a given water activity. The reaction will normally show a "switchlike" behavior, continuing in one direction until at least one reactant has passed completely into solution. If the solid-to-solid synthesis is favorable, the equilibrium yield will be maximized by choice of a solvent in which the solubility of the starting materials is minimized. Some of the dependencies predicted by our equations can be seen in data from our own studies or in the literature. This includes a linear decrease in yield with the reciprocal of the initial amount of reactants suspended in a fixed volume.