Physiological models are useful tools in the understanding of organic solvent toxicokinetics. An approach is presented where a physiological model is designed and solved by means of a spreadsheet macro instruction on a personal computer. The spreadsheet template is easy to use. Model parameters are entered and stored in tabular form, and any parameters and variables may be plotted. The model may be changed by editing the spreadsheet template, allowing compartments to be added, nonlinear metabolism to be introduced, etc. Accordingly, the kinetics of any substance and its metabolites, and any route of exposure may be modeled. The spreadsheet approach of physiologically based kinetic modeling is illustrated by simulating inhalation exposure to four organic solvents (acetone, 2-butoxyethanol, methylene chloride and styrene) in humans at various work loads. The results of the simulations are graphically compared with experimental data. By separating resting and working muscle tissue, the model successfully predicted the solvent concentrations not only in arterial but also in venous blood samples at various work loads (shown for acetone and methylene chloride).