The pharmacokinetic basis for the design of toxicity tests is discussed with reference to the absorption and clearance of drugs. The absorption and clearance of a wide range of drugs by laboratory animals and man has been examined and reviewed to provide a firm basis against which new drugs can be compared. Some pitfalls in either the empirical approach to toxicology or the incorrect interpretation of kinetic data are highlighted. An approach is outlined for the rational application of animal pharmacokinetic data in the assessment of the safety in man of a new therapeutic agent.