Fractional tubular reabsorption (FTR) of free and acyl carnitine was measured in 15 patients with various selective tubular transport defects and in 19 patients with more generalized tubular dysfunction (Fanconi syndrome). FTR of free carnitine was normal in all patients with a selective tubulopathy, FTR of acyl carnitine was normal in most, and plasma carnitine levels were normal without exception. In these patients, there was no evidence for the existence of a defective renal transport mechanism shared by carnitine. In the patients with Fanconi syndrome, mean FTR of free and acyl carnitine was low; their plasma carnitine levels were lowered and correlated with the FTR. In individual patients, FTR of free and acyl carnitine also correlated with the severity of the disease. In the group of Fanconi syndrome patients, FTR of free and acyl carnitine correlated linearly with that of valine. We concluded that the lowering of plasma carnitine in the patients with Fanconi syndrome was caused by excessive loss of carnitine in urine. Its pathophysiological significance remained to be established.