Individuals with chronic renal failure (CRF) have a high prevalence of protein-energy malnutrition. There are many causes for this condition, chief among which is probably reduced nutrient intake from anorexia. In nondialyzed patients with CRF, energy intake is often below the recommended amounts; in maintenance dialysis patients, both dietary protein and energy intake are often below their needs. Although a number of studies indicate that rats with CRF have increased protein catabolism in comparison to control animals, more recent evidence suggests that increased catabolism in CRF rats is largely if not entirely due to acidemia, particularly if these animals are compared to pair-fed control rats. Studies in humans with advanced CRF also indicate that acidemia can cause protein catabolism. Indeed, nitrogen balance studies and amino acid uptake and release and isotopic kinetic studies indicate that in nondialyzed individuals with CRF, who are not acidemic, both their ability to conserve body protein when they ingest low protein diets and their dietary protein requirements appear to be normal. For patients undergoing maintenance hemodialysis or chronic peritoneal dialysis, dietary protein requirements appear to be increased. The increased need for protein is due, in part, to the losses into dialysate of such biologically valuable nitrogenous compounds as amino acids, peptides, and proteins. However, the sum of the dietary protein needs for CRF patients (of about 0.60 g/kg/day) and the dialysis losses of amino acids, peptides and proteins do not equal the apparent dietary protein requirements for most maintenance dialysis patients. This discrepancy may be due to a chronic state of catabolism in the clinically stable maintenance dialysis patient that is not present in the clinically stable nondialyzed individual who has advanced CRF. Possible causes for such a low grade catabolic state include resistance to anabolic hormones (for example, insulin, IGF-1) and a chronic inflammatory state associated with increased levels of pro-inflammatory cytokines.