Pathological disruption of the intestinal mucosa increases the paracellular pathway, leading to an increase in the penetration of large molecules. Since growth hormone (GH) has a trophic intestinal effect, we used a double marker test to enable examination of intestinal permeability, which reflects the state of integrity of the intestinal mucosa. We recruited 22 adult patients, mean age 54+/-13.3 years, with GH deficiency due to partial or total hypopituitarism. None had received GH treatment at any time, although they were all in optimized replacement therapy. A control group was composed of 19 healthy age-matched relatives. The intestinal permeability test was performed with lactulose (5 g) and mannitol (1 g) after an oral load of 100 ml of aqueous solution. The urinary lactulose/mannitol ratio and the percentages of lactulose and mannitol excreted were determined on a 5-h urine collection. There were no significant differences between the patients and the control group in the lactulose/mannitol ratio (0.087+/-0.059 vs 0.077+/-0.064, respectively) or in the urinary excretion percentages of lactulose (0.067+/-0.048% vs 0.073+/-0.070%, respectively) or mannitol (5.127+/-3.269% vs 5.068+/-2.985%, respectively). In conclusion, no increase in intestinal permeability was detected in patients with GH deficiency, so that in spite of the known trophic effects of GH on the epithelial crypt cells, there was no intestinal hyperpermeability in these patients.