The effect of solvent on the activity of mushroom tyrosinase toward three substrates was studied at a constant water activity of either 0.74 or 0.86. No simple correlation was observed between enzyme activity and log P, but partition coefficients of substrate (P-S) and product (P-P) gave systematic relations with enzyme activity. When initial reaction rates were considered, there was a bell-shaped relationship between enzyme activity and P-S with an optimal P-S for each substrate. This can be explained by assuming that the solvent affected the enzyme activity primarily by affecting the substrate concentration in the aqueous layer around the catalyst where the enzymic reaction occurs. When long-term reaction rates were considered, a high P-P/P-S ratio was consistent with preservation of enzyme activity.