The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.