In this paper are discussed (1) the three general mechanisms by which radioisotopes may be retained in animal tissues long after labeled drugs are administered, (2) ways of differentiating these mechanisms, and (3) possible relationships between the toxic effects of drugs and their metabolism. It is emphasized, however, that studies on the disposition of drugs should be coordinated with toxicity studies in order to make the results of bioavailability and pharmacokinetic studies more meaningful in setting limits for food residues.