In our previous study, we reported the faster metabolism of intravenously administered furosemide, hence the smaller diuretic effect of furosemide in spontaneously hypertensive rats (SHRs) of 16 weeks of age than in the age-matched normotensive Wistar rats. In present study, in order to evaluate whether there is some alteration of the phase II metabolism including glucuronide and sulfate conjugations in 16-week-old SHRs and the age-matched Wistar rats, the pharmacokinetic parameters of acetaminophen (A), A-sulfate, and A-glucuronide were investigated after intravenous (iv) and oral 100 mg/kg administration of A to 16-week-old SHRs and the age-matched Wistar rats. After iv administration of A, the mean fraction of iv dose excreted in 24-h urine as A-sulfate (75.6 versus 67.8%) and the partial clearance of A to A-sulfate (8.10 versus 6.89 mL/ min/kg) were significantly greater in SHRs than in Wistar rats. Conversely, the mean fraction of iv dose excreted in 24-h urine as A-glucuronide (9.39 versus 15.0%) and the partial clearance of A to A-glucuronide (1.01 versus 1.49 mL/min/kg) were significantly smaller in these SHRs. Similar results were also obtained after oral dosing of A. The in vitro sulfotransferase activity toward A was significantly smaller (0.397 versus 0.331 microg/min/mg of protein) in 16-week-old SHRs than in the age-matched Wistar rats, whereas, the glucuronyltransferase activity toward A was not significantly different between these SHRs and Wistar rats. On the other hand, there was no significant difference in the both sulfotransferase and glucuronyltransferase activity toward A between 6-week-old SHRs and age-matched Wistar rats. Therefore, the alterations in sulfation and perhaps glucuronidation of A between 16 -week-old SHRs and normotensive Wistar rats suggested that some physiological factors derived from the chronic hypertensive status in SHRs might affect the disposition of drugs.