An impairment of gluconeogenesis has been proposed to explain the low arterial blood glucose of highlanders. Therefore, we studied splanchnic blood flow, splanchnic uptake of oxygen and lactate, and output of glucose in nine normal and six anemic highlanders at an altitude of 3,750 m. Splanchnic blood flow, arteriovenous difference for oxygen, and oxygen consumption were comparable at rest in both groups and in lowlanders from the literature, whereas splanchnic output of glucose, and uptake of lactate were approximately twice those in lowlanders. After 10 min of mild exercise in 12 subjects (7 normals, 5 anemic), no significant changes in splanchnic hemodynamics and metabolism were found. During 29% oxygen breathing in 8 subjects (5 normals, 3 anemics), arterial lactate, splanchnic uptake of lactate and output of glucose fell to normal sea-level values. We concluded that splanchnic hemodynamics are similar in adapted highlanders and in lowlanders, and that there is no evidence of an impaired gluconeogenesis at the altitude of the present study.