The non-invasive radiotracer technique positron emission tomography (PET) may provide valuable information in the toxicokinetic-toxicodynamic evaluation of endogenous or toxic environmental compounds. Assessment of mechanism of action of toxins is often difficult to validate. In this respect, PET may offer advantages since it can quantify not only the distribution and kinetics of the radiolabelled toxin in the body, but also the altered rates of physiological or biochemical processes induced by the toxin. It is even possible to validate the body distribution and tissue accumulation of the toxic compound in primates, since linear kinetics can be assumed after administration of the radiolabelled compound in minute amounts without any toxic or physiological effects. Quantitative estimates can be derived with accuracy and high precision. Using a multi-tracer protocol, it is often possible to illuminate both the kinetics and the dynamics of a toxic compound. Long-term effects of different toxins on dopamine receptor function have been evaluated with PET as well as the influence of Parkinson disease medication on pre- and postsynaptic dopaminergic receptor function over the course of the disease. In conclusion, PET may provide very informative insight into complex receptor interactions of both toxic compounds and drugs under development.