Hypothalamo-pituitary-adrenocortical activity in male homozygous and heterozygous Brattleboro rats was compared with that in normal (Long Evans) controls in an attempt to elucidate the role of vasopressin the control of the secretion of corticotrophin. 2. The concentrations of corticosterone and corticotrophin in the plasma, corticotrophin in the adenohypophyses and corticotrophin releasing factor in the hypothalami were lower in the heterozygotes than in the controls and lower still in the homozygotes. 3. The capacities of adenohypophyses and hypothalami to secrete in vitro corticotrophin and corticotrophin releasing factor respectively in response to trophic stimuli were also reduced in the heterozygotes and, to an even greater extent, in the homozygotes. 4. The results suggest that vasopressin is not the corticotrophin releasing factor but they do not exclude the possibility that it may be involved in the sequence of events which leads to the secretion of corticotrophin in the rat.