Re-Os isotopes have been measured on postorogenic potassic lavas from the Tibetan Plateau, the Betic domain of southeastern Spain, and the Colorado Plateau of the southwestern United States. Previous work has established that these lavas were all derived from parts of the subcontinental lithospheric mantle that had undergone metasomatic enrichment in incompatible elements, following various degrees of melt depletion. Cratonic depleted subcontinental lithospheric mantle peridotites typically have subchondritic 187Os/188Os; however, the postorogenic lavas are characterized by radiogenic 187Os/188Os ratios (0.139–0.559). Simple modeling shows that only very large degrees of melt depletion (>25%–30%) can lower source Re/Os ratios sufficiently to permit time-integrated development of subchondritic 187Os/188Os ratios. Such processes may have been largely restricted to the older Precambrian, and the peridotite component of the postorogenic lavas source was probably depleted by <25%. The more radiogenic values may reflect increasing contributions from metasomatic components or possibly crustal contamination. Our findings imply the need for caution in the use of Os isotopes as a diagnostic tracer of subcontinental lithospheric mantle contributions to lavas erupted through younger Proterozoic and Phanerozoic lithosphere.