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The Idrija Mercury Mine (1490-1994) appointed its first physician, Joannes Antonius Scopoli, in 1754. Most of his descriptions of mercurialism are still relevant today. This study highlights Scopoli's observations on the interaction between elemental mercury (Hg°) and alcohol, on the appearance of lung impairment, insomnia, and depressive mood in mercurialism. This presentation is based on Scopoli's experiences presented in his book, De Hydrargyro Idriensi Tentamina (1761), current knowledge, and our own experience acquired through health monitoring of occupational Hg° exposure. Some studies have confirmed Scopoli's observation that alcohol enhances mercurialism and his hypothesis that exposure to high Hg° concentrations causes serious lung impairment. Neurobiological studies have highlighted the influence of Hg° on sleep disorder and depressive mood observed by Scopoli. Although today's knowledge provides new perspectives of Scopoli's work on mercurialism, his work is still very important and can be considered a part of occupational medicine heritage. Am. J. Ind. Med. 53:535-547, 2010. © 2010 Wiley-Liss, Inc.