Since hypoglycemic responses to medium chain triglycerides (MCT) have been reported in adults we studied the effect of an acute oral load of lipids (2,8 g/kg) with 67% MCT on glucose homeostasis in 21 preterm infants in comparison to 14 age-matched control preterm infants. A hyperglycemic response from (mean +/- SEM) 57 +/- 1.1 to 74 +/- 2.5 at 30 min (p less than 0.01) and to 80.5 +/- 2.5 mg/dl at 60 min (p less than 0.01) was observed after administration of the lipids whereas no change in plasma glucose concentration was observed in the control group. After administration of the lipids there was no change in the concentration of insulin and glucagon in plasma. An intravenous glucose tolerance test (1 g/kg) was similar in the control group and 60 min after administration of the lipids. After administration of the lipids free fatty acid concentration remained unchanged while a significant decrease from 304 +/- 56 to 199 +/- 28 muEq/l was observed in 60 min in the control group. At 60 min beta-hydroxybutyrate concentration was higher after lipid administration (630 +/- 86 mumol/l) than in the control group (436 +/- 66 mumol/l) (p less than 0.05). A more rapid decrease in blood lactate concentration was found after lipid administration than in the control group while no change in plasma alanine concentration was observed in either groups. In five additional preterm infants, plasma glucose concentration increased from 56 +/- 0.6 to 75 +/- 0.9 mg/dl (p less than 0.01) 60 minutes after gastric administration of glycerol (0.3 g/kg). These data show that in preterm infants, a lipid load with 67% TCM produces a hyperglycemic response through gluconeogenesis without changing the peripheral rate of glucose disappearance.