A method for the simultaneous determination of extracellular fluid volume by radiosulfate-35 and total body water by tritiated water is described. Protein was precipitated from plasma with 10 per cent trichloroacetic acid. Radiosulfate-35 and tritiated water were counted in a dual-channel liquid scintillation spectrometer, using an automatic external standard to correct for quench. The sulfate space was calculated by the isotope dilution principle. Crossover counts contributed by radiosulfate-35 into the tritium channel were subtracted from the total counts in that channel. The tritiated water space was then calculated by the isotope dilution principle. Studies were performed in vitro and in 8 bilaterally nephrectomized rats. In vitro extracellular space by radiosulfate-35 and total body water by tritiated water demonstrated less than 3 per cent variation from the predicted volumes. In the rat, total body water determined with tritiated water demonstrated 4 per cent variation from that determined by desiccation. The method is simple, accurate, reproducible, and readily applicable for use in man and animals.