Male weanling guinea pigs were fed ad libitum a 3% pelleted casein diet supplemented with ascorbic acid while control animals were pair-fed a standard guinea-pig chow. Oedema was observed in some of the former group as early as the 2nd week and became very prominent by the end of the 3rd week. The malnourished group was characterized by reduced plasma albumin level and some disaggregation of hepatic polyribosomes but these showed no correlation in time with development of oedema. The pool of plasma essential amino acids were markedly reduced as early as Day 7, and most prominently affected were threonine, valine, isoleucine, leucine and arginine. Plasma histidine level was not significantly affected by malnutrition. Associated with early distortion of plasma aminogram was a pronounced increase (+176%) in free corticosteroid level by Day 7. Plasma concentration of aldosterone was significantly elevated in the malnourished guinea-pigs in comparison with the control group of the same age. Brain levels of free amino acids were not as extensively altered by malnutrition as was the case in plasma. At Day 7, only arginine, leucine and isoleucine among the essential amino acids, were significantly reduced while phenylalanine level was markedly increased. Histidine and its dipeptide homocarnosine as well as ornithine were the ninhydrin-positive substances in the brain most severely affected. By Day 14, the levels of histidine and homocarnosine were +71% and +58% respectively higher than the control values. Since the rate limiting factor in the synthesis of the putative neurotransmitter histamine in brain is the availability of the precursor amino acid histidine, the possible implications of pronounced increase in brain level of free histidine in experimental protein-energy malnutrition were discussed in the light of the known role of histamine as one of the neurotransmitters influencing the function of the anterior pituitary through regulation of release of the hypothalamic hypophysiotropic hormones.