The strontium and sulfur isotopic composition of barites has been analyzed to constrain the genesis of Ba and Ba-Pb-Zn ore occurrences in the Lower Cretaceous back-arc basin of the Atacama Region, northern Chile. The data support an origin by interaction of metal-bearing fluids having leached underlying volcanic rocks with the host carbonate (and evaporitic) rocks. A broad correlation between the strontium and sulfur isotopic composition and the typology of the barites suggest different degrees of interaction between the metal-bearing fluids and the host rocks.