New quinoline compounds were designed, synthesized, and examined with sub mitochondria. Most compounds showed high activity against NADH-ubiquinone oxidoreductase. Inhibition activity was mainly affected by the length of the lipophilic part, regardless of bulkiness or to ration of a phenyl group in the side chain. The β-methyl group was demonstrated to be the optimal functionality on tire nuclei of the quinoline derivatives so that either deletion or insertion of a methyiene on the group eliminated its activity(Received January 25, 1991, Accepted Mach 25, 1991).