In order to quantify the effect of human variability on a wide range of biological exposure indicators (EIs), a general compartmental model was developed and tested on several chemicals. The model consists of four compartments. In a first step, it was applied to four chemicals: toluene (TOL), phenol (Ph), lead (Pb), and mercury (Hg). Individuals were to be exposed 8 h a day, 5 days a week. Physiological parameter values were set to consider a physical workload of 50 W 12 h/day and at rest for the remaining 12 h. Monte Carlo simulations were carried out using realistic distributions of physiological and metabolic parameters. The variability extent index (VEI) and the main parameters of influence were determined for each of the EIs. The results were in agreement with literature data. The present compartmental model provides a fair description of the toxicokinetic (TK) variability of very different chemicals. It will, therefore, further be applied to investigate the variability of a wide range of biological indicators.