AbstractArbutin, hydroquinone‐O‐β‐d‐glucopyranoside (1) was found to inhibit the oxidation of l‐tyrosine (monophenolase activity) catalyzed by mushroom tyrosinase. However, arbutin itself was oxidized as a monophenol substrate at an extremely slow rate, and this oxidation was accelerated as soon as catalytic amounts (0.01 mm) of l‐3,4‐dihydroxyphenylalanine (l‐DOPA) became available as a cofactor. The result observed was supported by monitoring oxygen consumption. The depigmenting mechanism of arbutin previously reported is supportable if a cofactor is not available in the melanocytes. The combination with l‐ascorbic acid is a useful application, particularly when oxygen is limited. Copyright © 2004 John Wiley & Sons, Ltd.