Fasting could be an important factor in the induction of hypoglycemia in children with malaria because fasting results in a decrease in endogenous glucose production. The influence of extended fasting on plasma glucose concentration, glucose production, and gluconeogenesis were measured using [6,6-(2)H(2)]glucose and (2)H(2)O in 12 Surinamese children with severe malaria and compared with 16 children with non-severe malaria during a 16-hour controlled fast. Glucose concentration and glucose production were comparable after 8 hours of fasting and decreased in both groups (P < 0.001) with an extension of the fast up to 16 hours. Glucose concentration decreased faster in the non-severe group than in the severe group (P = 0.029). The decrease in glucose production was not different between groups (P = 0.954). Thus, fasting predisposes for hypoglycemia in young children with Plasmodium falciparum malaria. Hypoglycemia caused by fasting develops later in young children with severe malaria than in children with non-severe malaria.