Abstract: The method for determining blood volume has evolved substantially since first attempts were made in the latter part of the nineteenth century with the exsanguination of animals. The now accepted methods are based on indicator dilution methodologies. First attempts utilized inert dyes such as Evans Blue and Cardiogreen. These were found to be impractical due, primarily, to their rapid clearance from the blood. For many years, the most accepted method for blood volume determination was the dual isotope technique. This procedure utilizes chromium 51 or 99mTc to label autologous red cells and radioiodine 125 or 131 to label human serum albumin (HSA). Plasma and red cell volumes are measured separately and the results “combined”. The procedure requires on-site labeling of autologous red cells and HSA, and meticulous preparation of standards and doses. The complexity of this method leads to performance times of 6 to 8 hours. An FDA-approved single isotope method is now employed in over 60 major institutions. HSA is labeled with radioiodine 131 at an FDA radiopharmaceutical facility, and test doses and standards are provided to laboratories in kit form. The red cell volume is derived by a calculation utilizing the measured plasma volume and the value for the average whole-body hematocrit. All calculations are carried out by a dedicated microprocessor, and a final report is generated and printed. The results are compared with predicted normal values for male and female patients based on percentage deviation from normal weight. Preliminary results are available in 30 minutes and complete calculations in 90 minutes.