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The development of oral rehydration solutions (ORSs) has been one of the important therapeutic advances of this century. The optimal formulation, however, of ORSs for both cholera and other infective diarrhoeas is still debated. Part of the problem in developing ORSs has been the lack of adequate test systems for the assessment of new formulations before clinical trial. We have developed a jejunal perfusion, cholera toxin induced, secretory model in humans and have compared net water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l, glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310 mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed sodium secretion to absorption (p < 0.01). Both ORSs promoted net water absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium absorption rates were similar for both ORSs whereas chloride absorption mirrored sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a biologically relevant model of secretory diarrhoea, suggest it may be possible to achieve improved rates of rehydration by the use of hypotonic ORS with mid range sodium concentrations.