AbstractReaction rate constants for the catalytic step HLAD‐NADH + ketone → HLAD‐NAD++ alcohol in the HLAD‐catalyzed reduction of 3‐alkyl‐ and 4‐alkylcyclohexanones are determined from initial rate measurements in the coenzyme recycling system ketone‐ethanol‐NAD+‐HLAD. By rate measurements at several temperatures, activation parameters were determined and isokinetic relationships tracked down. Two different isokinetic relationships show that the 3‐alkylcyclohexanones pass through an other type of transition state than cyclohexanone and the 4‐alkylcyclohexanones, which means that they have a different arrangement on the HLAD‐NADH complex. The results are rationalized in view of the most recent principles on nucleophilic additions to carbonyl functions. The resulting model for the HLAD‐catalyzed reduction adequately explains the observed rate accelerating and decelerating effects and the stereochemist