Cardiovascular responses induced by drinking water are blood hypo-osmolality dependent, mediated by TRPV4 receptors in the periphery and osmoreceptors in the CNS acting through sympathetic autonomic efferents1,2, rather than being related to either blood volume loading, or gastric distension1. We investigated the effects of the temperature and hypoosmolality of ingested drinks on cardiovascular parameters in healthy human volunteers who ingested 300ml of either isotonic saline solution or water at either 37 or 6 0C (n=9, aged 24±3 years). Written informed consent was obtained, and the studies were approved by the University of Wolverhampton Life Science Ethics Committee. Factors known to alter autonomic balance were controlled. Following an acclimatisation period (≥20 min.), heart rate (HR) and blood pressure (BP) were continuously monitored using a Finapres device (Ohmeda Ltd). Lead 2 of 3-lead ECG and pneumotrace respiratory strap were used to record ECG and respiratory movements. Subjects’ ventilation was paced at 0.2 Hz, to standardise ventilatory function. Recordings lasted for 2 hours and were separated by at least one week. Five minutes of baseline recording were made prior to drink ingestion, followed by 5 minute recordings as various intervals. Cardiac vagal and sympathetic tone were assessed offline using time and frequency domain analysis of R-R interval variability and analysis of corrected QT interval (QTc).Cold saline decreased HR for 110 minutes (mean 2.035±0.26 beats/min reduction, p<0.01, paired t-test), with an increase in parasympathetic tone (mean 14.68±3.67 msec increase in RMSSD, p<0.01, paired t-test), with a concomitant reduction in systolic BP up to 20 minutes after ingestion (mean 11.5423±3.53 mmHg reduction in SBP, p<0.1, paired t-test). Conversely the combined hypo-osmolarity and cold effects of drinking cold water decreased HR for only 40 minutes (mean 3.15±0.86 beats/min reduction, p<0.01, paired t-test), with an increase in parasympathetic tone (mean 25.68±3.63 msec increase in RMSSD, p<0.05, paired t-test) and a fall in systolic BP up to 20 minutes after the drink (mean 5.8±0.45 mmHg reduction in SBP, p<0.1, paired t-test). Analysis of QTc following cold water ingestion indicated a shortening of QTc up to 80 minutes (mean 9.71±0.94 msec reduction in Qtc, p<0.01, paired t-test)3 after which it lengthened (mean 1.38±0.67 msec increase in Qtc, p>0.05, paired t-test) indicating a possible cardiac sympathetic withdrawal in the short term, but sympathetic reintroduction over the longer term. We conclude that the ingestion of the cold saline drink caused an increase in cardiac parasympathetic autonomic tone up to 110 minutes, but this was truncated with cold water drinking due to sympathetically mediated hypo-osmolarity effects leading to CVS parameters returning to near-resting levels.