The objectives of toxicokinetic (TK) studies are to evaluate systemic exposure of the toxicity species to drug and/or metabolite(s) and to relate exposure to dose level and toxicological findings. The tacit assumption is that such exposure can be related to target organ toxicity. Planning a TK program involves early development (often during discovery support) of an appropriate plasma assay, assurance that the studies conform to Good Laboratory Practices, evaluating exposure at steady state, and effective collaboration among toxicologists, kineticists, and other relevant disciplines. The 3 types of TK studies--prospective, concomitant, and retrospective--each have different goals. The various stages of TK program implementation range from those during drug discovery and selection to support of chronic toxicity studies. Exposure is best expressed as the area under the plasma concentration/time curve of drug and/or metabolite(s) and, for highly protein bound drugs, is based on the unbound fraction. Although the objectives of TK programs are generally standard and the Second International Conference on Harmonization has developed TK guidelines, the programs differ among pharmaceutical companies. Some variables in program design and implementation include properties of the drug, formulation used, characteristics of the target species, ability to develop a toxicokinetic-toxicodynamic relationship, strategies based on scientific/technical/philosophical considerations, dedicated resources, corporate support, and effectiveness of interdepartmental collaborations.