OBJECTIVE This study aimed to develop a physiologically based pharmacokinetic model for acetone and to predict the kinetic behaviour of acetone in the human body with that model. METHODS The model consists of eight tissue groups in which acetone can be distributed: the mucous layer of the inhaled air tract, the mucous layer of the exhaled air tract, a compartment for gas exchange (alveolus of the lung), a group of blood vessel rich tissues including the brain and heart, a group of tissues including muscles and skin that have low perfusion rates, a group of fatty tissues, an organ for metabolism (liver), and a compartment for urinary excretion (kidney). A mucous layer in the model is only the outermost layer of the mucus lining the wall of the air tract during inhalation and exhalation. To check the relevance of the model, the simulated results were compared with the experimental data. Next, simulation was conducted by changing the volume of the mucous layer and the respiratory rate to clarify the effect of these variables. Finally, simulation of an occupational situation was performed. RESULTS With an appropriate value for the volume of mucous layer, the simulated acetone concentrations in arterial blood, end exhaled air, urine, and fatty tissue were found to agree well with the experimental data. The volume of mucous layer and rate of respiration were critical for the appropriate simulation. The simulated occupational situation fitted the observed regression line in field studies quite well. The simulation also enabled predictions to be made about the characteristic kinetics for water soluble solvents. CONCLUSIONS The model is useful for understanding and explaining the kinetics of acetone.