Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal experiments show that much smaller amounts are required to reduce blood pressure (BP) when it is given intracisternally, or injected directly into the RVLM, compared to intravenous dose. Pretreatment with imidazoline I1 blockade from efaroxan abolishes the antihypertensive action of microinjection of moxonidine into the RVLM in the spontaneously hypertensive rat (SHR), while alpha2 blockade from SKF 86466 is much less effective. Microinjection of efaroxan into the RVLM prevents the fall of BP in the SHR from intravenous moxonidine. Moxonidine binds with an affinity for the imidazoline I1 receptor that is 33 times more effective than is alpha2-receptor binding. There is only a few fold preference for binding at the imidazoline I1-receptor for clonidine. Moxonidine results in a fall in adrenaline, noradrenaline and renin levels in humans, as might be expected from central inhibition of sympathetic tone. Moxonidine gives a fall of BP due to a decline in systemic vascular resistance, while the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. There is a reduction in left-ventricular end systolic and diastolic volumes. There is a regression of left-ventricular hypertrophy after moxonidine was given for 6 months. Following oral administration the half-life (Tmax) is about 1 h. Moxonidine is highly bioavailable, approaching 90%. Moxonidine is largely excreted unchanged, biotransformation is unimportant. It has a T(1/2) of 2.5 h, renal insufficiency prolongs the T(1/2). However, suggesting possible retention in the central nervous system (CNS) the antihypertensive effect lasts longer than would be expected from the half-life. Moxonidine has been shown to be suitable for administration once daily. Moxonidine is an effective antihypertensive drug. In the course of its evaluation it has been compared with representatives from each important class of antihypertensive drugs, with diuretics, both alpha- and beta-blocking drugs, clonidine, calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors. These studies have shown that BP control is overall similar with moxonidine and these other agents. Moxonidine has a favourable side-effect profile, at least in part due to its lack of effect on central alpha2 receptors.