We determined grain-scale heterogeneities (from 6 to 88 µg) in the stable carbon and oxygen isotopic compositions (δ13C and δ18O) of the international standard calcite materials (NBS 19, NBS 18, IAEA-CO-1, and IAEA-CO-8) using a continuous-flow isotope ratio mass spectrometry (CF-IRMS) system that realizes a simultaneous determination of the δ13C and the δ18O values with standard deviations (S.D.) of less than 0.05‰ for CO2 gas. Based on the S.D. of the δ13C and δ18O values determined for CO2 gases evolved from the different grains of the same calcite material, we found that NBS 19, IAEA-CO-1, and IEAE-CO-8 were homogeneous for δ13C (less than 0.10‰ S.D.), and that only NBS 19 was homogeneous for δ18O (less than 0.14‰ S.D.). On the level of single grains, we found that both IAEA-CO-1 and IAEA-CO-8 were heterogeneous for δ18O (1.46‰ and 0.76‰ S.D., respectively), and that NBS 18 was heterogeneous for both δ13C and δ18O (0.34‰ and 0.54‰ S.D., respectively). Closer inspection of NBS 18 grains revealed that the highly deviated isotopic compositions were limited to the colored grains. By excluding such colored grains, we could also obtain the homogeneous δ13C and δ18O values (less than 0.18‰ and less than 0.16‰ S.D., respectively) for NBS 18. We conclude that NBS 19, IAEA-CO-1, or pure grains in NBS 18 are suitable to be used as the standard reference material for δ13C, and that either NBS 19 or pure grains in NBS 18 are suitable to be used as the reference material for δ18O during the grain-scale isotopic analyses of calcite. Copyright © 2008 John Wiley & Sons, Ltd.