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Mount Isa is a major Australian and world Pb-Zn-Ag mineral province. The wide varieties of mineralization in the province are believed to be closely related to the geodynamic processes of Isan Orogeny, which occurred between ca 1500 and 1620 Ma. In order to understand the geodynamic processes associated with the Isan Orogeny and the giant mineralization systems in the Mount Isa district, a series of numerical models has been constructed to simulate coupled mechanical–hydrological processes, using Fast Lagrangian Analysis of Continua (FLAC), a finite difference computer code. The numerical modeling results have demonstrated that the most probable far-field stress orientation during the Isan Orogeny is the asymmetrical E–W shortening, which led to greater easternward tectonic movement at the west boundary of the district in comparison with westward movement at the east boundary. During the initial and early stage of the Isan Orogeny, the mechanical and hydrological conditions in the Leichardt Fault Trough of the West Fold Belt are much more favorable for fluid accumulation and mineralization than in the East Fold Belt. The Mount Isan fault zone developed as a high dilation shear zone where the fluids were focused. As the asymmetrical shortening progressed, shortening deformation and shear strain localization became intensified in the eastern part of the orogenic district. The eastern region therefore became a more favorable locality for hydrothermal mineralization. This structural development feature seems to explain why mineralization in the East Fold Belt is generally later than in the West Fold Belt. Fluid production from the Williams–Naraku granites could result in fluid over-pressuring, and this probably contributed to the extensive brecciation and related mineralization in the East Fold Belt. [ABSTRACT FROM AUTHOR]