Vapor-liquid partitioning coefficients for Cu and Zn in aqueous fluid were determined under boiling conditions at 500–650 °C and 35–100 MPa in sulfur-bearing and sulfur-free systems. A synthetic fluid inclusion technique was used to sample the experimental system of coexisting vapor-rich and liquid-rich fluid inclusions; the Cu and Zn concentrations in individual fluid inclusions were then analyzed by synchrotron radiation X-ray fluorescence. The vapor-liquid distribution constant of Cu [KDmCu(vapor)/mCu(liquid)], where = m denotes the molality of metal, is found to be strongly dependent on the sulfur content in the experimental solutions. In sulfur-bearing systems, Cu preferentially partitions into the vapor phase, whereas Zn preferentially fractionates into the hypersaline liquid. The KD values for Cu and Zn obtained in this study correspond well with those obtained from natural fluid inclusions in hydrothermal ore deposits. The results suggest that differential volatility of metals is an important factor affecting the enrichment of certain metals in different hydrothermal ore deposits.