SYNOPSIS. At low temperature (3°C), in the absence of substrate and cofactor, trout liver fructose diphosphatase (FDPase) is inactivated by exposures to relatively low pressures. FDP and Mg2+ protect against this inactivation; hence, maximum catalysis at pH 7.5 is pressure insensitive, while at more alkaline pH, it is markedly accelerated by pressure. The volume change of activation, ΔV*, at saturating FDP and Mg2+ concentrations is about −40 cm3/mole. The apparent Km for FDP and the Ka for Mg2+ are markedly increased by pressure. At low FDP or Mg2+ levels these kinetic properties outweigh ΔV* in determining the reaction rate; hence, under these conditions, piessure retards catalysis. Similarly, the K4 for AMP is notably pressure sensitive. Comparable effects of pressure on the kinetic constants for liver FDPase from benthic Corypliaenoides are much less pronounced, suggesting that in these off-shore species enzyme-substrate, enzyme-cofactor, and enzyme-modulator interactions have been tailored through evolution for pressure independent catalytic function.