OBJECTIVE To review studies of effects of antihypertensive agents on alterations in structure and function of small (resistance-size) arteries in hypertensive patients and in experimental hypertensive models, since these vessels may contribute to blood pressure elevation or to the complications of hypertension. METHODS The structure and endothelium-dependent relaxation of small arteries obtained in hypertensive humans from gluteal subcutaneous biopsies, and from different vascular beds in hypertensive rats, without and after antihypertensive treatment, and studied on a wire-myograph or as pressurized arteries, are described as reported in different studies. RESULTS Treatment of spontaneously hypertensive rats (SHR) with angiotensin converting enzyme (ACE) inhibitors, calcium channel antagonists, angiotensin receptor antagonists and novel beta blockers such as carvedilol, has been shown to result in regression of the altered structure of small arteries in different vascular beds, in addition to improved endothelium-dependent relaxation. Several studies in hypertensive patients have now shown that treatment with some ACE inhibitors (cilazapril and perindopril) or extended release calcium channel antagonists (nifedipine GITS) induces similar effects in small arteries obtained from gluteal subcutaneous biopsies: both structure and endothelium-dependent relaxation improve under treatment. In contrast, hypertensive patients with equally well-controlled blood pressure but treated with the beta blocker atenolol did not in any of three studies exhibit any improvement in the structure of small arteries or in endothelial function. CONCLUSIONS Although treatment for at least one year with some ACE inhibitors and extended release calcium channel antagonists corrects the structure and endothelium-dependent relaxation of gluteal subcutaneous small arteries, it still remains to be determined whether this apparently beneficial effect beyond blood pressure lowering of these and other agents with vascular protective properties will result in reduced morbidity and mortality in hypertensive patients.