Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid® [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters. Therefore, tissue carnitine deficiency, if present, would play only a minor role in the disturbed lipid metabolism of the uremic rat in the present experimental model.