The magma–ore deposit relationship of most low-sulfidation epithermal ore deposits is still unclear, partly because many stable isotopic studies of such deposits have indicated the predominance of meteoric waters within hydrothermal fluids. However, it is certainly true that hydrothermal systems are ultimately driven by magmatic intrusions, and epithermal gold deposits might therefore be produced by magmatic activity even in deposits having has no obvious links to a magma. We re-examine the genesis of two typical low-sulfidation epithermal gold deposits, the Kushikino and Hishikari deposits, using structural simulations and isotope data. Many epithermal gold deposits including the Kushikino and Hishikari deposits have been discovered in Kyushu, southwestern Japan. The Kushikino deposit comprises fissure-filling veins within Neogene andesitic volcanics that overlie unconformably Cretaceous sedimentary basement. The veins consist of gold- and silver-bearing quartz and calcite with minor amounts of adularia, sericite and sulfides. Although carbon and oxygen isotopic data for the veins indicate a meteoric origin of the ore fluid, finite element simulations suggest that the vein system might have formed in direct response to magma intrusion. In particular, geophysical data suggest that intruding magma has uplifted the basement rocks, thereby producing fractures and veins and a positive Bouguer anomaly, and providing the heat necessary to drive an ore-forming hydrothermal system. The second component of this study has been to investigate the nature and evolution of the Kushikino and Hishikari epithermal systems. Isotope data document the geochemical evolution of the hydrothermal fluids. We conclude that the existence of sedimentary basement rocks at depth might have affected the strontium and carbon isotopic ratios of the Kushikino and Hishikari ore fluids. The 87Sr/ 86Sr ratios and δ 13C– δ 18O trend reveal that major ore veins in the Hishikari deposit can be distinguished from shallow barren veins. It was suggested isotopically that fluids responsible for the barren veins in nearby shallow and barren circulation systems were only controlled by the shallow host rocks. Such multi-isotope systematics provide a powerful tool with which to determine the center of hydrothermal activity and thereby document the evolution of hydrothermal fluids.