Using the infusion of D-(-)-3-hydroxy-[1,2,3,4,-13C4]butyrate at tracer doses, we measured total ketone body turnover in 13 premature and 10 at term infants in the first 2 weeks after birth. The premature infants received parenteral and/or oral feeding. The normal newborns were either recently fed or briefly fasting. The premature and the fed at term infants had comparable concentrations of ketone body (476 +/- 86 and 406 +/- 78 mumol/l) and free fatty acids (FFA) (309 +/- 47 and 325 +/- 75 mumol/l). In the premature newborns, ketone body turnover rates (3.2 +/- 0.2 mumol kg-1 min-1) were 74% that of fed newborns at term (4.3 +/- 0.3 mumol kg-1 min-1, p < 0.05), and 18% that of normal newborns during a brief fast (17.3 +/- 1.3 mumol kg-1 min-1, p < 0.01). Ketone body production rates correlated with plasma FFA concentrations in both groups (r = 0.62 and 0.69, p < 0.05). However, for a similar plasma FFA content, ketone production was 2- to 3-fold lower in the premature, indicating an immature hepatic capacity to convert FFA into ketones. Our study therefore shows that ketogenesis is already active in infants born 10 weeks before normal term and continuously fed, but that daily ketone production is lower than at term.