In nine women studied serially before conception and through the first trimester, plasma osmolality (Posm) started to decline with the first missed menstrual period, was significantly decreased by the fifth week of pregnancy and was 10 mosmol/kg lower than preconception values by the tenth week, changing little thereafter. Changes in plasma sodium (and its attendant anion) accounted for the majority of the decrement. In separate studies, urinary concentration and dilution, assessed by water deprivation and loading, studied in nine women during their last trimester and again 10-12 weeks post partum. Basal Posm was 9 mosmol/kg lower in the last trimester than post partum (p less than 0.001) but the results of concentration and dilution tests were similar during and after pregnancy. Basal urinary arginine vasopressin (AVP) excretion was similar during and after pregnancy and water loading suppressed AVP excretion in both pregnant and postpartum women. An unanticipated observation was that lateral recumbency interfered with urinary concentration tests in both pregnant and postpartum women. The results demonstrate that the decrement in Posm during pregnancy is an early event. The data (urinary AVP excretion, its suppression by water loading and normal concentration and dilution despite a lower plasma tonicity) also suggest that human pregnancy is accompanied by a resetting of the threshold for vasopressin secretion to a lower Posm.