The effect of a dietary sodium restriction (15 mmol/day) on the development of adrenocorticotrophic hormone (ACTH) hypertension was examined in six normal male subjects. When ACTH (1 mg/day) was given for 5 days to subjects on a sodium-restricted diet, systolic blood pressure rose (116 +/- 4 to 125 +/- 4 mmHg, P less than 0.001), while diastolic blood pressure was unchanged. There was a modest antinatriuresis (cumulative Na+ balance, 59 +/- 2 mmol) which was reflected in a small rise in exchangeable body sodium (65 +/- 15 mmol); plasma concentrations of active renin and angiotensin II both fell during ACTH treatment. Plasma volume rose (2.8 +/- 0.2 to 3.6 +/- 0.16 l, P less than 0.01) while extracellular fluid volume was unchanged. Plasma concentration of atrial natriuretic peptide (ANP) rose to more than twice basal. Glomerular filtration rate (inulin clearance) increased (111 +/- 9 to 131 +/- 7 ml/min, P less than 0.001), renal plasma flow, measured as the rate of para-aminohippurate (PAH) clearance, was unaltered and calculated filtration fraction rose. Dietary sodium restriction did not, therefore, prevent an ACTH-induced increase in blood pressure. The increase in plasma volume with ACTH is not dependent on renal sodium retention and is associated with increased concentrations of ANP. When these data are compared with findings previously reported in subjects given the same dose of ACTH when on normal or high sodium intakes, it is clear that, although the action of ACTH in raising blood pressure is not dependent on exogenous sodium or extracellular fluid volume expansion, sodium retention can modify the level of blood pressure attained.