The pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors are often difficult to characterize using standard tools. Most of the problems arise from the tight binding of ACE inhibitors to ACE. The present paper discusses how tight binding of ramiprilat to ACE affects the pharmacokinetic characteristics and in vitro measurement of ACE inhibition. Data from a randomized crossover study in healthy volunteers given 2 different dosage forms with 5 mg ramipril serve to compare the theoretically deduced predictions with actual measurements. The data confirm that elimination is concentration-dependent and that therefore the pharmacokinetics are non-linear. Renal clearance increases with concentration. With respect to pharmacodynamics, free ramiprilat depletion due to tight binding is the reason for the steep nature of concentration-effect curves often observed for ACE inhibition. This type of relationship, however, cannot be described by the classical Emax model nor by the sigmoid Emax model. The model of tight binding presented shows that the concentration-effect curve becomes steeper the larger the concentration of ACE and the greater the affinity of the inhibitor to the target molecule. With the classical Emax model the concentration can be doubled about 3 times to increase the measurable effect from 10 to 50% maximum effect, and because the relationship is symmetric at the EC50% point of inflection, the concentration can be doubled another 3 times to increase the effect from 50 to 90%. With the tight-binding concentration-effect relationship, doubling the concentration about 3 times may also increase the effect from 10 to 50% of the maximum effect, a further doubling of the dose, however, causes a steep increase of the effect from 50 to nearly 100%. This tight-binding concentration-effect relationship may also be present in other classes of drugs.