2-Hydroxypyridine-N-oxide (HOPNO) is described as a new and efficient transition-state analog (TS-analog) inhibitor for the mushroom tyrosinase with an IC50 = 1.16 mu M and a K-I = 1.8 mu M. Using the binuclear copper(II) complex [Cu-2(BPMP)(mu-OH)](ClO4)(2) (2) known as a functional model for the tyrosinase catecholase activity, we isolated and fully characterized a 1:1 (2)/OPNO adduct in which the HOPNO is deprotonated and chelates only one Cu-atom of the binuclear site in a bidentate mode. On the basis of these results, a structural model for the tyrosinase inhibition by HOPNO is proposed.