Adult rats kept for eleven weeks on a diet deficient in protein lost weight and some developed scrotal oedema. The retention of bromsulphthalein was increased, but the thymol turbidity test was unaffected; the apparent plasma volume was increased.Water diuresis in the protein deficient animals was impaired. There was no apparent delay in the mean rate of water absorption from the whole gastro-intestinal tract although a delayed absorption of water from the intestine was found in some animals. The concentrations of total plasma proteins and plasma albumin were low as compared with normal animals, but the plasma sodium levels were within normal limits. The inulin clearance (glomerular filtration rate) of the animals on the protein-deficient diet was significantly lower than that of the controls.In normal rats, aminophylline and acetazolamide were diuretic. Caffeine and sodium benzoate did not increase the urine output and mersalyl was antidiuretic. In the protein deficient rats, cortisone acetate increased the water diuresis. Caffeine and sodium benzoate, aminophylline and acetazolamide did not significantly increase this response, mersalyl had an antidiuretic effect. Cortisone acetate increased the food and water intake of the protein deficient rats; it also increased the glomerular filtration rate.It is now well established that animals kept on low protein diets have an impaired water diuresis (Dicker, Heller, and Hewer, 1946;Heller and Dicker, 1947;Leslie and Ralli, 1947; Guggenheim and Hegsted, 1953;Schnieden and Blackmore, 1955a). Rats kept on a protein deficient diet also have an increased total body water and are oedematous (Haigh and Schnieden, 1956). We have investigated the effects of diuretics on such animals to see whether water diuresis could be restored. In addition to the conventional drugs (mercurial and xanthine diuretics), cortisone and corticotrophin were also tested because these hormones have a diuretic effect in nephrosis (Luetscher, Deming, Harvey, Lew, and Poo, 1950; Luetscher, Deming and Johnston, 1951 Bergeim, 1942) 4.5, cod liver oil 3.0, supplemented by 50 mg. vitamin B complex powder (Crookes Laboratories/100 g. diet. It contained 0.4% thiamine, 0.5% riboflavine, 0.18% pyridoxine, 4% nicotinamide, and 0.0014% pantothenic acid. 3 mg. tocopherol acetate/100 g. diet was also added. This diet provided approximately 300 cal./100 g. and 0.2 protein/100 cal.Measurement of Food Intake.-The daily intake of food was estimated by placing groups of 6 rats in suspended cages. Weighed amounts of food in excess of the daily requirement were provided. Some scattering of food could not be prevented, so the cages were suspended over a tray lined with filter paper and the scattered food separated from the faeces each morning and added to food not consumed.Measurement of Water Intake.-Rats were placed in individual metabolism cages fitted with graduated drinking tubes. The amount of water drunk by each animal in 24 hr. was noted.Plasma Prateins.-A biuret method was employed for estimation of total plasm...