The disposition of adenosine 5'-phosphosulfate (APS), an endogenous nucleotide, was investigated in rats. The degradation of APS in rat plasma was very rapid. APS was degraded in rat plasma to AMP and ATP, and these nucleotides were further degraded through adenosine. The degradation kinetics was examined. For the in vivo study, the method to protect APS from degradation in blood was examined, and it was found that the addition of EDTA to APS-containing blood and storage at 4 degrees C can protect against APS degradation. After intravenous bolus injection, APS in plasma declined rapidly and the rate of elimination was dose-dependent: the biological half-life was about 2s at the dose of 0.3 mg/kg and was longer at 3 mg/kg. When APS was administered by intravenous infusion, the plasma level rapidly reached a steady-state, which then rapidly declined after the infusion was stopped. The total body clearance of APS could not be fully explained by metabolism in plasma or glomerular filtration, therefore the contribution of other elimination processes to the total body clearance was suggested.