Total body nitrogen (TBN) is mainly sequestered within the metabolically active lean body mass, in close relationship with total body potassium (TBK). TBN and TBK of growing children manifest superimposed accretion rates, display a sexual difference at the onset of adolescence and during adulthood, thereafter decreasing in elderly subjects. Plasma transthyretin (TTR) follows a comparable profile from birth to death in healthy individuals. Uncomplicated protein-energy malnutrition primarily affects the activity of nitrogen metabolic pool, reducing protein syntheses to levels compatible with survival. This adaptive response is well identified by declining TTR concentrations. In various stressful conditions, in vivo responses are characterized by upregulation in injured regions and with muscle proteolysis exceeding protein synthesis, resulting in a net body negative nitrogen balance. Again, this evolutionary pattern mirrors that of plasma TTR. Attenuation of stress and/or introduction of nutritional rehabilitation allows restoration to normal of both TBN and TTR values that follow parallel slopes. Despite distinct etiopathogenic mechanisms, TTR concentrations appear to reflect the loss or gain of TBN in body pools and they predict later outcome in malnutrition and in conditions of acute and/or chronic inflammation.