OBJECTIVE: To investigate the renal handling of carnitine in preterm and term ill neonates. METHODS: We studied the fractional tubular reabsorption of carnitine and the proximal renal tubular function of infants in the first week of life who were receiving very little or no carnitine in their diets. RESULTS: Mean plasma levels were low: total carnitine was 16.4 +/- 7.0 mumol/L, free carnitine was 9.2 +/- 5.0 mumol/L, and acylcarnitine was 7.2 +/- 4.1 mumol/L. The most premature group of neonates (gestation age, 26 to 31 weeks) had a fractional tubular reabsorption rate of free carnitine of 94.3% +/- 3.3%, which was lower than in the other two groups (98.1% +/- 2.4% for gestational age 32 to 36 weeks, p = 0.001; and 99.2% +/- 0.6% for gestational age 37 to 42 weeks, p = 0.002). In all patients the fractional tubular reabsorption of acylcarnitine was lower than that of free carnitine, indicating possible tubular secretion of acylcarnitine. It correlated with the total plasma carnitine levels (r = 0.53; p = 0.002). The fractional tubular reabsorption of free carnitine also correlated with gestational age (r = 0.60; p < 0.001). CONCLUSIONS: Ill neonates have a fractional tubular reabsorption rate of free carnitine within the normal range. It increases with gestational age, and has the same maturation rate as the other known indexes of proximal tubular function.