A method has been developed for the in situ determination of Re-Os isotopes in single grains of sulfides in mantle-derived peridotites using a laser ablation microprobe attached to a multicollector-induced coupled plasma mass spectrometer (MC-ICPMS). High-precision Os isotope analysis by MC-ICPMS is demonstrated by the measurement of interlaboratory Os standards. Evaluation of mass bias correction procedures shows that the exponential law provides the best fit to the Os isotope data and that the ratio of the mass fractionation coefficients for Re and Os remains constant for the range of typical instrument operating conditions. This relationship enables the accurate and precise correction of the isobaric interference of 187Re on 187Os for 187Re/188Os values up to 1.6.Results are presented for single sulfide inclusions in olivine macrocryts from kimberlites in the Siberian and Slave Cratons, and sulfides enclosed in silicates and interstitial to silicates in peridotite xenoliths from the Slave Craton and Massif Central, France. Enclosed sulfides larger than 50 μm in diameter and with Os contents ≥40 ppm give 187Os/188Os ratios with a precision of 0.1% (2 SE), which is equivalent to N-TIMS whole-rock data. Interstitial sulfides typically have lower Os (10 to 30 ppm) and give analyses with lower precision (∼1 to 2%) but still provide valuable information on the movement of Os within the lithosphere. The sulfide inclusions in silicates preserve significantly less radiogenic Os isotopic compositions than interstitial sulfides and accordingly produce significantly older and more realistic Re-Os age information. Whole-rock Os isotope compositions reflect the proportions of different generations of enclosed and interstitial sulfides; this calls into question the significance of many published "depletion ages."