A simple procedure for the preparation of soluble human succinate dehydrogenase is described. These preparations have proved suitable for analysis by zone electrophoresis, using a specific stain to detect activity after separation. In a survey of succinate dehydrogenase from various tissues and different individuals, no evidence for genetic heterogeneity due to the expression of either multiple loci or alternative alleles at the succinate dehydrogenase locus was found. However, epigenetic heterogeneity in both molecular size and charge was seen and various explanations for the occurrence of the isoenzymes are explored. Estimates of molecular size (93,300 +_ 9100) suggest that the smallest active unit of succinate dehydrogenase accounts for the major part of the solubilized activity. Kinetic studies have shown that the apparent Km values for succinate (0.9 mM) and PMS (0.4 raM) are comparable to those previously described for the beef heart enzyme, and these parameters were not significantly altered when the enzyme was removed from the membrane milieu. However a marked non-succinatedependent activation of the membrane-associated enzyme at 38 C is apparently lost on solubilization, and this observation may have some bearing on earlier reports o fan apparent decrease in Vma x on solubilization of succinate dehydrogenase.