The effect of mannitol infusion on the renal physiology, was evaluated in experimental animals and in man. In animals plasma flow and glomerular filtration rate were determined by the PAH extraction and by the innulin clearance technique. In patients renal blood flow measurements were carried out using the Xenon133 washout technique. Baseline studies were obtained and repeated following the intravenous infusion of 20% mannitol. A significant increase in total renal blood flow could be demonstrated in experimental animals, but only a minimal increase of total flow was demonstrated in man following the infusion of mannitol. This observation suggests that the diuretic effect of mannitol is very likely due to the osmotic effect in the tubule causing increased interstitial renal pressure rather than by an increase of actual renal blood flow. This observation is supported by the clinical experience that mannitol remains a powerful diuretic in even hypotensive patients with low renal blood flow.