After intraperitoneal injection of a tracer dose of d-xylose-1- 14C into guinea pigs, 10.8 ± 2.0% (mean ± one standard deviation) of the radioactivity was recovered as expired 14CO 2 in 4 hours and 41.3 ± 3.0% as urinary 14C in 5 hours. Approximately 60% of the urinary 14C exhibited chromatographic properties identical to those of authentic d-xylose; the remainder migrated as a single unidentified compound. After injection of d-xylose-1- 14C into nephrectomized guinea pigs, a mean of 28.3% (range 23.0–32.0) of the radioactivity was recovered as 14CO 2 in 6 hours. In vitro studies revealed that kidney and liver oxidize d-xylose-1- 14C to 14CO 2. Liver extract catalyzed the conversion of d-xylose to d-xylonic acid with pyridine nucleotide as a cofactor. Evidence is presented to show that this enzyme activity differs from hepatic glucose dehydrogenase. d-Xylonic acid-1- 14C was oxidized to 14CO 2 by intact guinea pigs. Slices of kidney and liver, and homogenates of kidney carried out this oxidation in vitro. These observations support the possibility that the oxidation of d-xylose by the guinea pig involves its initial conversion to d-xylonic acid and subsequent decarboxylation.