The clinical pharmacology of clonidine has been studied using a sensitive specific method of drug analysis and quantitative measures of cardiovascular and other drug effects. The plasma concentration effect relationship for dry mouth and sedation is log linear until a maximum effect is achieved. The relationship of plasma level to hypotensive effect in man and animals shows a positive correlation over a narrow concentration range up to 1.5--2.0 ng/ml. At higher plasma levels a reversal of hypotension occurs with hypertension at concentrations over 10 ng/ml. This "therapeutic window" may reflect actions of clonidine on alpha receptors in the brain stem which lower blood pressure counteracted by peripheral effects of vascular alpha receptors which causes hypertension. Information on the pharmacokinetics and dynamics of clonidine can assist in optimising this form of antihypertensive therapy.