Regular physical activity provokes numerous adaptations in the gastrointestinal tract and liver. It has been suggested that these changes may alter the pharmacokinetics of drugs in humans. We addressed this suggestion by measuring paracetamol pharmacokinetics in a group of healthy young males chosen to represent the widest possible range of habitual physical activity and food intake. Daily caloric intake in the 19 men, obtained from 3-day dietary records, ranged from 1680 to 5110 kcal (21 to 66 kcal/kg). Each volunteer ingested paracetamol 1000mg in the fasted, resting state in the morning; antecubital venous blood samples were analysed for the parent compound and its glucuronide and sulfate conjugates by high-performance liquid chromatography for 6 subsequent hours. We found no evidence that paracetamol pharmacokinetics vary with physical activity or with caloric intake: (a) for the parent compound, there was no correlation in maximum blood concentrations, half-life, total clearance, or area under the curve with individual caloric intake, and (b) when volunteers were divideda prioriinto more active and less active groups, ora posterioriinto higher and lower calorie consumers (a 70% difference in daily caloric intake), these groups had identical plasma disappearance curves for paracetamol itself and for both of its metabolites. We conclude that the enormous variation among humans in long term physical activity and food intake fails to alter any aspect of the appearance or disappearance of paracetamol from blood.