The Pb–Zn deposit at Sant'Antonio di Val d'Aspra in the Farma Valley (Southern Tuscany) is hosted by Lower Moscovian carbonate rocks and shows many characters commonly found in Mississippi Valley type (MVT) deposits. Ore minerals (essentially sphalerite and galena) are closely confined to dolomitized portions of an only partly preserved black limestone. Mineralized carbonate rocks appear to have been eroded before the deposition of the overlying Upper Moscovian (Late Podolskian) shales. The diffuse presence of structures frequently found in internal sediments of karstic cavities indicates that supergene mechanisms have played an important role in the history of the deposit. A fluid inclusion study carried out on ore and gangue minerals revealed the presence of two different types of inclusions. The homogenization temperatures ranged from 120°C to 225°C but the most frequently found values were around 170°C. Salinity ranged from moderately low values up to 20 eq. wt. % NaCl. Lead isotopic composition rules out any relationship between the Sant'Antonio mineralization and Tertiary hydrothermal base metal occurrences in the same area. When all the data are taken together, a contrast is evident between geo-petrographic and isotopic data on the one hand, and fluid-inclusion microthermometry on the other.