L-Carnitine is an essential cofactor in transfer of long-chain fatty acids across the inner mitochondrial membrane. L-Carnitine is present in living systems in free form and as short-chain and long-chain fatty acylcarnitine esters. In recent years, several clinical syndromes due to or associated with carnitine deficiency have been described. They include 2 primary types--systemic and muscle (or myopathic) carnitine deficiency--and at least 15 syndromes in which carnitine deficiency seems to be secondary to genetic defects of intermediary metabolism or to other conditions. Possible beneficial effects of exogenous carnitine in ischemic heart disease have been the focus of intensive research in recent years. Free carnitine and esterified carnitine are measured by a sensitive enzymatic-radiochemical method. In some cases, the diagnosis of carnitine deficiency can be made by assay of total (free plus esterified) carnitine in plasma or serum. Proper diagnosis, however, often depends on determination of total carnitine in skeletal muscle or liver (or both). Since the first clinical description of carnitine deficiency in 1973, considerable progress has been made in defining and classifying the carnitine deficiency syndromes. Recent efforts in basic and clinical research have provided important clues about the molecular causes of these syndromes.