ArylamineN-acetyltransferases (NATs) play an important role in both the detoxification of arylamine and hydrazine drugs and the activation of aryl-amine carcinogens. Because the catalytic triad, Cys-His-Asp, of mammalian NATs has been shown to be essential for maintaining protein stability, ren-dering it impossible to assess alterations of the triad on catalysis, we explored the impact of the highly conserved proximal residue