Abstract Coupling between deformation processes and rock permeability is a major factor influencing fluid migration and fluid-rock interaction during the formation of mesothermal lode gold systems in mid- to upper crustal regimes. The evolution of permeability during deformation is controlled by a dynamic competition between deformation-induced porosity creation processes and porosity destruction processes. Localization of deformation in faults and shear zones leads to flow localization, with large scale flow systems forming when active faults and shear zones link to create percolation networks. Broad regions of fluid focusing develop around the upstream segments of active shear networks and fluid discharge regions develop in the downstream parts of these systems. The architecture of flow within shear networks is influenced by the relative proportions of backbone, dangling and isolated structures within the network. Connectivity in the network may increase with growth of the shear network, but is expected to continually change as the locus and intensity of deformation changes. The typical distribution of mesothermal lode deposits within crustal scale shear networks indicates that mesothermal systems might develop most efficiently in networks that are close to the percolation threshold, i.e. with most flow occurring along a flow backbone forming only a small part of the total shear network. Dangling elements adjacent to the backbone, particularly in the downstream (discharge) parts of the system, provide some of the best potential for gold deposition by fluid-rock interaction processes. Contrasting styles of fluid flow are expected between the seismogenic and aseismic regimes of the shear- or fault-hosted hydrothermal systems associated with mesothermal lode gold formation. Below the seismic-aseismic transition, creep processes can lead to near-steady state permeabilities and produce continuous fluid flow regimes. In the seismogenic regime, large cyclic changes in fault permeability, fluid pressures and fluid flux occur during the seismic cycle, and lead to fault-valve behaviour and episodic fluid flow. The seismogenic regime allows for a richer variety of gold deposition processes than is generally available in the aseismic regions of hydrothermal systems associated with lode gold formation.