The concept that the concentration of a drug in plasma bears a relationship to its concentration at the receptor site initially excluded those drugs which form an irreversible attachment to their receptor and those drugs which act via a series of active metabolites. In this latter group, the plasma concentration of a parent drug is only remotely related to its pharmacological effect. Further work in man and animals has shown that in general, plasma levels of drugs are a better indicator of toxic and therapeutic effects than empirical dosage schcdules. Gradual development of techniques has refined our concept of so-called desirable or therapeutic ranges of drugs and enables us to correlate toxic manifestation with drug plasma concentration in many instances. At present the use of plasma drug levels is an invaluable adjunct in medical treatment. It is used in the evaluation of new drugs to compare dose equivalence and dose response by relating effect to plasma levels in early phases. It is used in the pharmacokinetic evaluation of drugs which is necessary to estimate absorption, distribution, metabolism, elimination of drugs, as well as measuring free and bound concentrations, and relationship of plasma levels to tissue concentration whenever practicable. These studies indicate persistence of the drug in plasma but they must be interpreted with caution because biological effect and half life pharmacokinetics are not necessarily identical. Certainly dose-schedules and frequency of administration are guided to some extent by a knowledge of these parameters. In comparing routes of administration both in the evaluation and therapeutic use of a drug, plasma levels give useful information on the bioavailability i.e. the proportion of drug available to the body and indirectly to the receptor after an oral administration compared to that achieved after I.V. dosing. Most importantly it enables the clinician to tailor the dose to individual requirements. The fundamental reason why plasma levels are an essential part of modern drug therapy is that individual rates ofdrug metabolism vary widely. This is largely genetically determined and it is impossible to predict from a given dose of a drug its bioavailability in an individual. Variation in handling of drugs is often related to a corresponding variation in the biological effect.