The heterogeneity of lactate dehydrogenase was first recognized when Neilands (1952) demonstrated activity in each of the two electrophoretically distinct proteins, previously separated by Meister (1950) from the crystalline ox-heart enzyme. Subsequently Vesell and Bearn (1957) found three distinct components when human sera were subjected to starch-block electrophoresis, and Sayre and Hill (1957) obtained similar results with paper electrophoresis and gradient-elution chromatography. About the same time Wieland and Pfleiderer (1957) found that most organs contain up to five protein fractions each exhibiting lactate dehydrogenase activity. Soon afterwards it was appreciated that the isoenzyme composition of the serum was of considerable diagnostic value (Vesell and Beam, 1958a, 1958b; Hess, 1958; Wieme, 1959), and this gave a tremendous impetus to further study of variations in the isoenzyme content of the blood serum.