Conventional methods for measuring the concentration of deuterium in body fluids are by either isotope ratio mass spectrometry or Fourier transformed infra-red transmission (FTIR) spectroscopy. The latter method is often preferred as it is less expensive and time consuming; however, having a lower sensitivity means a larger sample volume is required. This study investigated an alternative FTIR spectroscopic method, attenuated total reflection Fourier transformed infra-red spectroscopy (ATR-FTIR), which has the potential to provide shorter analysis times while requiring smaller sample volumes. Deuterium was assayed by ATR-FTIR in plasma in the concentration range 0.5 to 2.5 mg mL-1, typical of those observed in tracer dilution measurements of total body water. Minimal sample preparation was required and analysis time was substantially decreased compared to transmission FTIR. Samples were analysed with high precision (CV < 0.5 %). Precision of assay was maintained when assaying plasma volumes of only 10 ïL. The application of the method to the determination of total body water in humans and animals (horses) was demonstrated. A rapid and simple method for the measurement of deuterium in plasma is described that only requires very small sample volumes, rendering the method suitable for use in paediatrics where blood sampling is required to be kept to a minimum.