Water drinking activates the autonomic nervous system and induces acute hemodynamic changes. The actual stimulus for these effects is undetermined but might be related to either gastric distension or to osmotic factors. In the present study, we tested whether the cardiovascular responses to water drinking are related to water's relative hypoosmolality. Therefore, we compared the cardiovascular effects of a water drink (7.5 ml/kg body wt) with an identical volume of a physiological (0.9%) saline solution in nine healthy subjects (6 male, 3 female, aged 26 +/- 2 years), while continuously monitoring beat-to-beat blood pressure (finger plethysmography), cardiac intervals (electrocardiography), and cardiac output (thoracic impedance). Total peripheral resistance was calculated as mean blood pressure/cardiac output. Cardiac interval variability (high-frequency power) was assessed by spectral analysis as an index of cardiac vagal tone. Baroreceptor sensitivity was evaluated using the sequence technique. Drinking water, but not saline, decreased heart rate (P = 0.01) and increased total peripheral resistance (P < 0.01), high-frequency cardiac interval variability (P = 0.03), and baroreceptor sensitivity (P = 0.01). Neither water nor saline substantially increased blood pressure. These responses suggest that water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiac vagal tone. That these effects were absent after drinking physiological saline indicate that the cardiovascular responses to water drinking are influenced by its hypoosmotic properties.