Mineralised vein systems have been investigated at nine localities at the southern margin of the Anglo-Brabant fold belt in Belgium. During the late Silurian to early Middle Devonian Caledonian orogeny, shear zones formed, inferred to be associated with granitoid basement blocks in the subsurface. The circulation of a metamorphic fluid, possibly originating in the Cambrian core of the fold belt, along these shear zones resulted in the formation of mesozonal orogenic mineralisation at the southern margin of the Anglo-Brabant fold belt. The fluid had a composition dominated by H2O-CO2-X-NaCl-KCl. The shear zones form part of a greater fault zone, the Nieuwpoort-Asquempont fault zone, which is characterised by normal faulting that started before the Givetian and by the reactivation of the shear zones. Two fluid generations are associated with this normal faulting. First, a low salinity H2O-NaCl(-KCl) fluid migrated through the Palaeozoic rocks after the Silurian. Based on the isotopic composition, this fluid could be a late-metamorphic Caledonian fluid or a younger fluid that originated from the Rhenohercynian basin and interacted with Lower Devonian rocks along its migration path. Second, a high salinity H2O-NaCl-CaCl2 fluid was identified in the fault systems. Similar fluids have been found in southern and eastern Belgium, where they produced Mississippi Valley-type Zn-Pb deposits. These fluids are interpreted as evaporative brines that infiltrated the Lower Palaeozoic basement, from where they were expelled during extensional tectonism in the Mesozoic.