Pig heart lactate dehydrogenase (EC 1.1.1.27; H4 isoenzyme) has been subjected to the action of beef spleen cathepsin D (EC 3.4.23.5) at pH 3.9. No proteolytic effect on the tetrameric form of the dehydrogenase could be detected. On the other hand, the acid proteinase appears to act on the dissociated monomers in such a manner that they are unable to reassociate into functional tetramers. This finding could be correlated with proteolytic modification of the monomers. The extent of proteolysis depends on the temperature and duration of the incubation.