A technological development is described through which the stable carbon-, oxygen-, and nonexchangeable hydrogen-isotopic ratios (δ 13 C, δ 18 O, δ 2 H) are determined on a single carbohydrate (cellulose) sample with precision equivalent to conventional techniques (δ 13 C 0.15‰, δ 18 O 0.30‰, δ 2 H 3.0‰). This triple-isotope approach offers significant new research opportunities, most notably in physiology and medicine, isotope biogeochem-istry, forensic science, and palaeoclimatology, when isotopic analysis of a common sample is desirable or when sample material is limited. A s the most abundant biopolymer, cellulose represents an important substrate for isotopic investigation. Variations in the relative abundance of the stable carbon, oxygen, and nonexchangeable hydrogen isotopes from which the cellulose is made are inextricably linked to the global carbon and water cycles. As a consequence, the isotopic study of these elements, both as labeled compounds and at natural-abundance levels, has contributed significantly to the characterization of plant-physiological processes and the study of past and contemporary environmental changes. 1−5 This environmental and physio-logical linkage between carbon-, oxygen-, and hydrogen-isotope fractionation means that, when viewed together, these three indicators have the capacity to provide far greater insights into plant physiology and the functioning of the Earth system than might be possible if considered in isolation. An improved understanding of this three-way relationship is of increasing importance in the evaluation and development of dynamic vegetation and water-isotope models, as the measurement of stable isotopes in natural archives (e.g., tree rings, peat macrofossils, pollen) can provide a unique perspective on isotopic variability across spatial and temporal scales not accessible from direct observations or remote sensing. 4−10