The rates of utilization and oxidation of glutamine and glucose by oesophageal and duodenal tissues have been investigated in both rats and human subjects. In the rat, glutamine utilization by oesophageal tissue was 2–3-fold lower than that in the duodenum, and this substrate contributed less than 10 % to the total oxidative metabolism of the tissue, even when glutamine was the only substrate provided. In contrast, rat duodenal tissue derived about 34 % of the total CO2 production from glutamine-C, and this contribution was not suppressed by the addition of either glucose or a mixture of the other substrates. Rates of glucose utilization and oxidation by the duodenum were lower than those for glutamine, and were significantly (P<0·001) suppressed by addition of glutamine. In both oesophageal and duodenal tissues, less than 10 % of the glutamine-C utilized was fully oxidized, approximately 60–70 % was converted to glutamate, and 30–40 % to alanine. Results obtained using human biopsy tissue samples were similar to those observed in the rat. Glutamine oxidation contributed 34 (sd 4) % of the total CO2 production by the duodenal tissue, but only 8 (sd 4) % to oesophageal tissue oxidation. The findings suggest that glutamine is not an important or preferred fuel for oesophageal tissue, whereas it is for duodenal tissue. Thus, these tissues can be expected to respond differently to glutamine administration.