To investigate the role of L-carnitine in medium-chain fatty acid (MCFA, fatty acids with 6-12 carbons) metabolism, 16 newborn pigs were fitted with umbilical arterial catheters. Pigs were placed in respiration chambers, and [1-14C]MCFA were infused for 9-12 h providing energy equivalent to 50-175% of the animals' metabolic rate. After 5-7 h (carnitine-free infusion period) of MCFA infusion, a primed (12.5, 25 or 50 mumol) co-infusion of L-carnitine [5, 10 or 20 mumol/(h.kg0.75), respectively] was started and maintained for 4-5 h (carnitine infusion period). The fatty acid oxidation rate (MCFA-derived CO2/total CO2 x 100) was calculated based on the specific radioactivity of expired CO2 (measured per 20-min interval) and the specific radioactivity of the MCFA infused. A single-pool exponential curve was fitted to the fatty acid oxidation rate of the carnitine-free infusion period and was extrapolated to the carnitine infusion period. For each piglet, the average difference between fatty acid oxidation rate during the carnitine infusion period and the extrapolated curve was calculated and tested for significance using a t test. Under steady state conditions, MCFA oxidation accounted for 40% of MCFA infused. Carnitine, independent of the level, increased the fatty acid oxidation rate by as much as 20% if the energy provided as MCFA exceeded 50% of the metabolic needs of the pig (P < 0.01), and the response above 50% was proportional to the relative rate of fatty acid infusion (increase in fatty acid oxidation rate = -3.9 + 0.07 x infusion rate, r0.76).(ABSTRACT TRUNCATED AT 250 WORDS)