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In a previous paper based on the same study (1), it was shown that the serum urea concentration of subjects with intact renal function increases with protein consumption. In contrast, the serum creatinine concentration in such subjects was shown to be independent of protein consumption (2). It has long been known that endogenous urea excretion increases with the protein consumed, while the rate of endogenous creatinine excretion has been shown to be relatively independent of the amount of protein consumed (3).Popper and Mandel (4) first utilized the endogenous creatinine clearance in man as a measure of the glomerular filtration rate. Steinitz and Turkand (5) found a good correspondence between the inulin and endogenous creatinine clearances in normal subjects. More recently Brod and Sirota (6) have studied the endogenous creatinine chromogen/inulin clearance ratio in man, and concluded that the endogenous creatinine clearance corresponds closely to the inulin clearance in normal subjects. Discrepancies which appear in subjects with renal disease and markedly impaired renal function, are not sufficient to affect seriously the clinical value of the test as a general indicator of renal competence. This judgment has been confirmed by Camara (7), as well as by numerous clinical observations of our own.Miller and Dubos (8) showed that creatinine is not the only chromogen in human serum that produces color in the Jaffe reaction. The ratio of such "pseudocreatinine" to creatinine is higher in azotemic individuals. Brod and Kotatko (9) found that the endogenous creatinine and the inu- lin clearances approach identity only when the "true" creatinine clearance is used. They used Lloyd's reagent to adsorb creatinine and determined the residual "pseudocreatinine" concentration in the serum.Diurnal variations in the endogenous creatinine clearance have been studied by Brod (10). He found that the endogenous creatinine clearance in normal individuals is depressed during the night. In a more complete investigation, Sirota, Baldwin and Villarreal ( 11 ) studied diurnal variations in renal function of normal male subjects. They found no significant difference in the night and day values for the endogenous creatinine clearance, except for a slight fall in the period from 12 Midnight to 4 A.M. These experiments were conducted on "routine ward" diets, and no attempt was made to vary or to control at a constant level the consumption of protein or of creatininecontaining foods.Of all renal function tests, the endogenous creatinine clearance is easiest to perform since no foreign substance is infused, the serum concentration is constant, and urine collections can be made over long periods of time, up to 24 hours, thus minimizing the errors in collection. Those who have struggled with the methods for performing inulin determinations realize the relative precision and simplicity of the creatinine determination, as modified by Bonsnes and Taussky (12). For these reasons it seemed desirable to investigate the effect of dietary protein con...