In order to throw light on the nature of uremia, many investigators have studied the physiologic effects produced when urea is administered to or injected into animals. The majority of those who have undertaken such studies were unable to demonstrate that urea acted as a poison. Only a few have succeeded in producing definite toxic effects. For example, Herter and Wakeman,1 as well as Marshall and Davis,2 found that approximately 1 per cent. of the body weight must be injected into animals in

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... der to produce a fatal result. Ascoli,3 in reviewing the earlier literature, has sought to explain the occasional toxic effects observed on one or more of the following assumptions: (1) the urea used was not pure, (2) it was injected intravenously in too concentrated a solution, or (3) where used in dilute solution the effects were attributable to the excessive amounts of liquid rapidly introduced into the body. Under any circumstances it is clear that in animal experiments definite toxic effects can be produced only when extraordinarily large doses of the drug were given, doses which presumably raise the concentration of urea in the body above that which is encountered in most cases of uremia in man. For these reasons the view has become generally accepted that the toxic effects of urea in any concentration encountered in patients are negligible and that the symptoms of uremia are due to the action of the other and more poisonous substances. Recent advances in our knowledge concerning the toxic symptoms presented by patients in the more advanced stages of nephritis permit one, however, to approach this question from a new point of view. It seems established that uremia, in the sense of any toxic state com-