To study the effects of microgravity on the mechanisms involved in the regulation of body hydrous status, total body water (TBW), plasma volume (PV), and its main regulating hormones (plasma renin, aldosterone, atrial natriuretic peptide (ANP), anti-diuretic hormone (ADH)) were determined, by isotopic dilution, Dill and Costill's formula, and radio-immunologic dosages, in 9 male subjects submitted to a 90-d head-down bed rest (HDBR). ADH was determined in 24 h urinary collection as well as osmolality, sodium, and potassium. Body mass decreased (-2.8 +/- 0.8 kg) as well as TBW(-7.2% +/- 0.9%, i.e., -2.6 +/- 0.7 kg) and PV (-4.7% +/- 1.8%). Renin and aldosterone were enhanced (+109.0% +/- 15.4% and +87.2% +/- 38.9%, respectively). Simultaneously, we observed a decrease in ANP (-33.2% +/- 20.4%). Other variables, including ADH, were not affected by HDBR. Body mass and TBW decrease (and consequently lean body mass) are associated with muscle atrophy. Renin, aldostrerone, and ANP modifications are well explained by the decrease in PV, which was not enough to induce ADH changes. It suggests that in man, the main regulatory factor for ADH secretion is osmolality, when PV is modestly and progressively decreased without arterial pressure modification, which was the case in the present protocol.