Mammals are ureotelic and respond to an increased protein intake with an increase in glomerular filtration rate and renal plasma flow. Birds and terrestrial insects are uricotelic and following a high protein intake increase tubular urate secretion by the kidney (birds) or Malpighian tubule (insects). Ureogenic fish given NH(4)Cl increase gill and renal clearance of urea and gill clearance of ammonia. Renal mass increases in mammals, birds and reptiles given a high protein intake. Thus, animals in general respond to an increase in protein intake with a change in excretory function such as to increase the clearance of the major nitrogenous end-products of protein metabolism. The components of this general animal excretory response include; a redistribution of regional perfusion with increased renal and gill blood flow, increased GFR and gill ammonia clearance, increased renal tubular urate clearance, changes in urea transport protein abundance and/or function and renal hypertrophy. Animal groups differ as to which components are accentuated. Amino acid catabolism with generation of ammonia appears to be a necessary prerequisite for this excretory response to occur. A hypothesis is put forward that ammonia itself is a regulatory molecule and an important signal communicating between amino acid catabolism following an increase in protein intake and the sequence of events leading to a change in excretory function.