Carnitine metabolism was studied in normal-weight and obese subjects by measurement of carnitine and its acyl derivatives in plasma and urine. When first fed an isocaloric, low-carnitine diet, both groups showed a decrease in plasma total carnitine, primarily due to a decrease in the free carnitine fraction. Urinary free carnitine excretion also fell significantly. When fasting was instituted, plasma total carnitine concentration increased. This was the net result of a rapid increase in short-chain and long-chain acylcarnitine and a delayed decrease in free carnitine. Urinary excretion of short-chain acylcarnitines increased parallel to rising plasma concentrations, whereas free carnitine excretion first decreased and then tended to increase slightly. Both plasma and urinary short-chain acylcarnitine correlated with beta-hydroxybutyrate. All of these changes were reversed by refeeding, in the obese even with a low-carnitine hypocaloric intake. Obese subjects also developed hyperketonemia significantly more slowly than did normal-weight subjects, yet demonstrated substantially the same changes in magnitude and direction in carnitine and its metabolites.