Abstract: This study examined the absorption and disposition of orally administered acetaminophen in morbidly obese patients as compared to subjects of normal weight, and possible changes in disposition as the patients underwent weight reduction through dietary modification. The overall disposition of acetaminophen was not affected by a weight loss of 8 to 30 kg; elimination half-life, time to reach the peak, and peak plasma concentration varied within each subject but not in a systematic way. The half-life was the same in the obese patients (2.6 ± 0.85 hours) and normal subjects (2.6 ± 0.12 hours). However, maximum plasma concentrations were reached at a significantly later time and were significantly lower in the obese patients as compared to the normals, implying an apparently lower absorption rate. The area under the plasma concentration-time curve for the obese patients when normalized to ideal body weight was more consistent with that in the normal subjects than when normalized to total body weight. Administration of a normal dose of acetaminophen to an obese patient should yield plasma levels in the same range as persons of normal weight. As total weight may exceed 200 per cent of the ideal weight in this patient group, dosing according to total rather than ideal weight could lead to toxic or lethal effects when using the 10 mg/kg dosing recommendation.