The disposition of acetaminophen after oral administration was investigated in adults with cystic fibrosis (n = 5) and in age-matched healthy control subjects (n = 5). The total plasma clearance of acetaminophen was found to be greater (p less than 0.025) in subjects with cystic fibrosis (0.362 +/- 0.081 L/hr/kg) than in control subjects (0.247 +/- 0.022 L/hr/kg). This difference in clearance was found to be primarily attributable to a greater metabolic clearance of acetaminophen to acetaminophen sulfate (0.080 +/- 0.023 L/hr/kg for subjects with cystic fibrosis and 0.045 +/- 0.008 L/hr/kg for control subjects; p less than 0.05) and to a greater metabolic clearance of acetaminophen to acetaminophen glucuronide (0.189 +/- 0.051 L/hr/kg for subjects with cystic fibrosis and 0.114 +/- 0.017 L/hr/kg for control subjects; p less than 0.05) in persons with cystic fibrosis. Of the mechanisms that may be responsible for these differences, the most likely is enhanced activity (in subjects with cystic fibrosis) of the transferases that mediate the metabolism of acetaminophen to acetaminophen sulfate and acetaminophen glucuronide, respectively.