We describe an accurate method for the determination of K and Ca using isotope dilution inductively coupled "cold'' plasma mass spectrometry (ID ICP-MS). Measurements were applied to the certification of K and Ca in a new oyster tissue standard reference material, SRM 1566b, and the determination of Ca for an international measurement comparability exercise for serum. Measurements were made using an ICP-MS operated in the cold plasma mode. Molecular ion interferences arising from the plasma were reduced below 1000 counts per second (cps) for the isotopes of interest, while maintaining a sensitivity of better than 9 6 10 6 cps for a 1 mg L-1 Ca solution. Detection limits of 1.3 ng L-1 and 2.5 ng L-1 were obtained for K and Ca, respectively. Isotope ratio measurement repeatability of the Ca-40/Ca-42 and K-39/K-41 ratios for spiked samples was better than 0.2% relative (n = 5, 1 s). Though interference from background peaks was reduced, molecular ions arising from the oyster tissue and serum matrices caused spectral interference. Reduction of the matrix induced interference was successfully accomplished using cation exchange chromatography. Data that demonstrate the reproducibility and accuracy of the ID ICP-MS measurements are presented. A split sample comparison with thermal ionization mass spectrometry (TIMS) was performed.