In children with acute falciparum malaria gluconeogenesis fails to compensate in the presence of decreased glycogen breakdown, resulting in decreased glucose production and hypoglycaemia. In adults glucose metabolism has not been studied in detail. Recently we developed a new method to measure gluconeogenesis in vivo by incorporation in glucose of deuterated water ( 2 H 2 O). To evaluate glucose production and gluconeogenesis in malaria, we studied 7 adult Vietnamese patients with uncomplicated falciparum malaria (age 28 ± 2 years) and 7 healthy Vietnamese adults (age 29 ± 1) in the postabsorptive state. Glucose production was measured by infusion of d 2 -glucose and gluconeogenesis by incorporation of deuterium after oral administration of 2 H 2 O. Plasma enrichments were measured by mass spectrometry.Results: (mean ± SE); Plasma glucose concentration was 4.74 ± 0.19 mmol/l in the patients and 4.23 ± 0.16 mmol/l in the controls (P = 0.08). Basal glucose production was higher in the patients: 3.03 ± 0.25 vs. 2.42 ± 0.06 mg/kg/min (P = 0.04). Gluconeogenesis was increased in the patients (1.92 ± 0.21 vs. 0.97 ± 0.03 mg/kg/min (p = 0.002), representing 63 ± 3% vs. 40 ± 2% of total glucose production (P = 0.002). Glycogen breakdown was decreased in the patients compared with the controls (1.11 ± 0.11 vs. 1.43 ± 0.07 mg/kg.min, P = 0.06).Conclusion: In postabsorptive, adult patients with uncomplicated malaria average basal glucose production is increased by 25% and gluconeogenesis by 100% compared to healthy controls. Glycogen breakdown is decreased by 30%. Therefore, glucose metabolism in malaria is regulated differently in children from that in adults, which may explain the higher incidence of hypoglycaemia in children with falciparum malaria.