The heat shock protein, heme oxygenase-1 (HO-1), contributes to the protection of the intestine. Some experimental models suggest that induction of HO-1 by glutamine may contribute to the preservation of intestinal mucosa. The effect of an enteral infusion of glutamine for 6 h on HO-1 expression in duodenal mucosa was studied in healthy men and women and compared with an isonitrogenous mixture of amino acids. After enteral infusion, endoscopic duodenal biopsies were performed and either fixed in formalin for immunohistochemistry or frozen for HO-1 mRNA analysis by reverse transcriptase-polymerase chain reaction. Histologic examination revealed that HO-1 was constitutively expressed in intestinal epithelial cells (IEC), and that glutamine increased the grade of HO-1 immunostaining (P </= 0.01). Glutamine also increased the percentage of HO-1 immunoreactive lamina propria cells (LPC, 10.5 vs. 7.5%, P </= 0.05). Glutamine significantly increased HO-1 mRNA expression compared with control amino acids: median (range) 156 (102-182) vs. 100 (68-179)%, P </= 0.05. The mRNA level for HO-1 was correlated with the percentage of immunoreactive LPC (r = 0.55, P = 0.017) and the grade of immunostaining in IEC (r = 0.51, P = 0.030). In conclusion, glutamine enhanced HO-1 mRNA and protein expression in human duodenal mucosa. These data support further evaluation of the effects of glutamine on intestinal HO-1 during states of intestinal inflammation.