This laboratory was established in 1970. The first phase of work was to develop the tracer dilutions for measurement of total body water (TBW), extracellular water (ECW), exchangeable sodium and plasma volume in animals. The second phase was to apply these techniques in human studies. Most of the tracers used in the early studies were radioactive materials, however, since 1999, only non-radioactive tracers have been used for measurements. In 1999, the main instruments used in this laboratory were upgraded with the latest models, and the measurement precision was significantly improved to ±1.0% for TBW measurements and to ±1.3% for ECW measurements. The laboratory has developed study packages for TBW and ECW measurements that contain tracer dose, specimen collection tubes, and instructions for performing the measurement and for specimen shipment. The study package can be shipped to any location in the world for investigators to administer the tracer dose, collect the specimens and mail back to the lab for analysis. The study packages can be prepared according to special requirement based on study population and research design. For example, the laboratory measures tracer concentrations in saliva instead of plasma in pediatric subjects. The laboratory has performed more than 7000 TBW and 5000 ECW measurements in many research projects and clinical trials and has served as the central laboratory for studies involved multiple sites. The laboratory has provided services to investigators across the USA, and also to investigators in Canada, Europe, and South-America. The laboratory has trained many scientists from Europe and Southern America. The telephone number for this laboratory is 212 523-3394. Background and Applications for Tracer Dilution Studies History Three isotopes of water are recognized in nature, deuterium, tritium, and oxygen-18 labeled water. Schloerb et al. were the first to measure total-body water in 1951 using the isotope deuterium. The methods importance greatly increased after the report of Pace and Rathbun in 1945 indicating that water existed in a relatively stable proportion to fat-free mass, approximately 0.73. This subsequently led to the widespread use of total-body water as means of estimating fat-free mass and total-body fat in both animals and humans. Application The method is relatively straightforward and simple to apply. Subjects ingest a known amount of isotope, and at some later time point the isotope remaining in the body is quantified. The water compartment is then re-sampled through urine, saliva, or blood. Total-body water is then calculated using the classic dilution formula. Details of the procedure vary depending on isotope used, analytical method, and accuracy desired. Deuterium is relatively inexpensive to purchase, simple to measure in secretions and blood samples, and safe as the isotope is stable. The isotope tritium is also inexpensive, easy to measure in blood samples, and exposes the subject to a small amount of radiation. Today deuterium is usually favored as an isotope for water dilution over that of tritium because of radiation exposure with tritium and the increasing ease with which deuterium can be measured in samples. Oxygen-18 labeled water is relatively expensive and measurement is possible only in specialized laboratories that have mass spectroscopy equipment. Oxygen-18 labeled water is useful for measuring total-body water when carrying out doubly labeled water studies of energy expenditure. Once the dilution space is known from the evaluation protocol, total-body water mass must then be calculated. The dilution spaces of deuterium and tritium are slightly larger than actual total-body water as proton exchange with other organic constituents increase the apparent volume of distribution. Most investigators today assume the overestimate of total-body water by deuterium and tritium is approximately 4%. A correction for water density is also required when converting from water volume to water mass. The oxygen-18 space is also slightly larger that actual total-body water by about 1% in most studies. Some investigators thus assume that oxygen-18 represents an even more accurate assessment of actual total-body water, the oxygen exchange being substantially less than that of the proton exchange for deuterium and tritium. The technical error of total-body water measurement varies depending on the specific protocol applied. However, most approaches allow reliable measurement of total-body water with a technical error in the range of 1% to 3%. Assuming subjects are healthy weight stable adults, the proportion of fat-free mass as total-body water is relatively stable at 0.73. Some variability in this ratio is recognized across age groups and in various disease states. The advantage of total-body water as a means of estimating fat-free mass and total-body fat is that the method is simple, relatively inexpensive, and easy to carry out even in isolated settings. The disadvantage of the method is that dilution protocols often require several hours and subject conditions can be very variable depending on hydration status, the presence of disease, or ambient conditions such as environmental temperature. Hydrometry is the only approach capable of measuring extremely large subjects who weigh over several hundred kilograms. Similarly hydrometry is widely applied in the study of large animals including whales and other aquatic mammals.