Antihypertensive drugs affecting the renin-angiotensin system (RAS) can be evaluated in single-dose studies in healthy volunteers challenged with angiotensin I or II, or in subjects in whom the RAS has been activated by salt depletion. Such pharmacological studies can be used to investigate dose-response relationships. The relevance of these models in predicting therapeutic dose range has been evaluated by comparing the results of pharmacological studies with those of a conventional dose-finding study in hypertensive patients with the new AT1-receptor antagonist olmesartan medoxomil. In healthy volunteers, 2.5–40 mg olmesartan medoxomil single doses significantly inhibited the pressor response to exogenous angiotensin I. A dose-response relationship was observed, with relevant (> 75%) inhibition occurring at doses of 10 mg and above. In a single-dose crossover study in patients with mild-to-moderate hypertension receiving a sodium-restricted diet, statistically significant lowering of mean 24-h blood pressure, measured by ambulatory blood pressure monitoring, was observed at doses of 10–80 mg. By comparison, a large-scale (n = 792), placebo-controlled, dose-ranging study in patients with mild-to-moderate hypertension likewise showed significant superiority over placebo for 10–80 mg olmesartan medoxomil once-daily doses. Single-dose clinical pharmacology studies provided an accurate indication of the effective dose range of a new AT1-receptor antagonist. Such models can be useful in identifying, for more detailed study, the likely therapeutic dose range of new drugs acting on the RAS. However, the dose-response still requires testing in large target populations.