A combined study of mineral O and Rb-Sr isotopes was carried out for a number of Mesozoic granitoids in China in order to compare the degree of O isotope equilibrium between coexisting minerals, with the validity of mineral Rb-Sr isochrons for granitoids. A scrutiny of both O isotope geothermometry and Rb-Sr internal isochron dating for corresponding minerals indicates that equilibrium O isotope fractionation between Rb-Sr isochron minerals corresponds to geologically meaningful isochron ages if the variation in 87Rb/86Sr ratio is big enough to provide reasonably small uncertainties in age. Significant deviation of the Rb-Sr isochron age from the actual age appears to depend on the difference in Sr isotopic composition between an external fluid and the igneous minerals. As a result, O isotope disequilibrium is often caused by interaction between the rock and the external fluid that results in mineral alteration. Post-magmatic alteration can cause isotope exchange between the minerals and an internally buffered fluid that is isotopically identical to the host rock. The O isotope composition of coexisting minerals in studied samples changed principally due to a decrease in temperature. Both Rb and Sr concentrations and the Sr isotope ratios of isochron minerals also changed due to the mixing of different Sr reservoirs. Nevertheless, the isochron age can remain unchanged if the mixing took place along the isochron chord between the internal fluid and the minerals from that newly altered minerals formed. This provides an insight into the effect of internal and external fluids on the validity of mineral Rb-Sr chronometry. In addition, an alternative approach is proposed to construct the cooling curve by a combined use of O isotope temperature and mineral isotope age for the granitoids of interest. Comparing with the traditional method using the empirical closure temperature for Rb-Sr chronometry, the proposed approach utilizes fewer variables with smaller uncertainties than the traditional way. © Springer-Verlag 2006.