Gut health maybe envisaged as the ability to continue to function i.e. withstand, large fluctuations in lumen conditions. We developed a standardized test to quantitatively assess the response of the gut to a standardized noxious stimulus. Twenty healthy carefully screened female volunteers (9 smokers and 11 non smokers) were recruited. They each received 600mg of aspirin or placebo in random sequence and were subsequently dosed with 10g lactulose and 5g mannitol. Half hourly urine samples were collected over six hours. Urinary sugar concentrations were determined by HPLC using a method similar to Trehan et al. Lactulose mannitol ratios (LMR) and rates of excretion of lactulose and mannitol were found to be normally distributed and were compared by doubly repeated measures ANOVA.The magnitude of the LMR depended significantly on the period over which the urine was collected, the six hour period being significantly higher than the three hour collection period (d.f. 1,19; F = 48.74; P <0.001). Dosage with 600mg aspirin caused a significant increase in LMR (d.f. 1,19; F = 23.95; P < 0.001) over the six hour period of collection. Variation in LMR over time was driven by differences in the patterns with which the two probes were absorbed and excreted. Greater quantities of mannitol were excreted during the first three hours than the subsequent three hours (d.f. 1.19; F = 48.88; P < 0.001) of collection, with the excretion rate peaking at 1.5 to 2 hours post dosage. The pattern of excretion of mannitol was unchanged after dosage with aspirin. Lactulose excretion over the six hour period was maintained at a similar rate but the overall rate was significantly increased after dosage with aspirin (d.f. 1,18; F = 16.83; P = 0.001). There were no differences in the patterns of excretion of the two probes between smokers and non smokers. The LMR test can reproducibly detect increases in permeability resulting from a 600mg dose of aspirin, particularly when the patterns of absorption of the component sugars are considered in relation to the duration of the sampling period. It remains to examine whether the test is able to identify agents that promote the recovery of permeability from, or reduce the response to, the dose of aspirin.