Protein-Film voltammetry reveals the global effects of H/D isotopic substitutions, both in organic substrates and solvent, on bidirectional catalytic electron transport in a mitochondrial respiratory enzyme, succinate dehydrogenase. The voltammetry is controlled by the enzyme kinetics and therefore provides a direct display of the characteristic relationships between turnover rates (current) and driving force (potential). This enables simultaneous measurement of relative electron-transport rates for oxidative and reductive directions alongside thermodynamic data (reduction potentials) relating to substrates and active sites. Measured over a range of pH and pD, the relationships between effective catalytic potentials of the enzyme and formal reduction potentials for substrate and active-site yield a ''potential-domain'' description of the catalytic energetics, which complements and extends the picture obtained by conventional kinetic methods. For the organic substrates, a marked decrease is observed in the rate of oxidation of perdeuteriosuccinate compared to-succinate, but there is no change upon deuterating fumarate. Can changing the solvent from H2O to D2O there is a significant decrease in catalytic activity, particularly in the direction of fumarate reduction. Simultaneously, the characteristic potentials of the enzyme (active-site FAD and effective catalytic potentials) are raised but to a lesser extent than is the reduction potential of the substrate. The catalytic energetics are thus altered. For the first time with a complex redox enzyme, the results enable H/D substitution effects to be rationalized in terms of the changes introduced in overall driving force and enzyme reduction potentials, as well as the effects of intrinsic kinetic processes.