A B S T R A C T When normal individuals eat 0.33 g protein N/kg body weight (BW)3' per day, they excrete 10-15 mg urea N/h per kg BW3'4. If they now ingest (at 0 h) 0.27 (dose A), 0.40 (dose B), 0.53 (dose C), 0.94 (dose D), or 1.33 (dose E) g protein N/kg BW3' (in the form of casein, ovalbumin, or lactalbumin), the rate of urea N excretion accelerates within 4 h. At dose C a maximal rate of urinary urea N excretion (MRUE) is reached, which averages 55 mg urea N/h per kg BW3' and which persists for 16 h. Higher doses of protein do not further accelerate urea excretion, but prolong the duration of MRUE to 28 h (after dose E). Blood urea N (BUN) rises by [7][8][9][10][11][12][13][14][15][16][17][18][19][20] mg/100 ml during the first 8 h after dose C to E, and remains stable within ±5 mg/100 ml during the ensuing 8-28 h of MRUE. Each increment of protein above dose C causes a further increment in plasma a-amino N. During infusion of free amino acids at a rate of 110 or 165 mg amino acid N/h per kg BW3' for 12 h, rate of urea excretion increases to the MRUE value produced by dose C-E of oral protein.These findings indicate that MRUE corresponds to a period of maximal rate of urea synthesis (MRUS). MRUS is greater than MRUE because one fraction of newly formed urea is hydrolyzed in the gastrointestinal tract, and another fraction may accumulate temporarily in body water during the MRUE period. Oral neomycin reduces the proportion of urea hydrolyzed in the gut to less than 20%; its extent is measured by recovery in the urine of a tracer dose of ["4C]urea injected intramuscularly during determination of MRUE. Accumulation of urea in body water is estimated from increment in BUN during the period of MRUE measurement (8-24 h after dose E of casein) and from body water