Objective Studies of cerebral arterioles have suggested that pulse pressure may be a more important determinant of small-artery structure than systolic, diastolic or mean blood pressure in stroke-prone spontaneously hypertensive rats and in rats with an arterio-venous shunt. A study of small arteries has suggested that this is not the case in human essential hypertension. We therefore investigated the role of hemodynamic determinants on small-artery structure in hypertensive patients. Design and methods To determine whether pulse pressure contributes to structural alterations in human essential hypertension, small arteries (lumen < 300 mu m) were obtained from gluteal subcutaneous biopsies of 40 normotensive subjects aged 40.7 +/- 1.2 years and 45 untreated essential hypertensive humans aged 46.5 +/- 1.3 years. The relationship between the media: lumen ratio of the small arteries and levels of systolic, diastolic and mean blood pressure and pulse pressure was investigated. Results The media:lumen ratio (5.33 +/- 0.001%) of small gluteal subcutaneous arteries of normotensive subjects was significantly smaller and the lumen diameter (306 +/- 13 mu m) significantly larger than in untreated hypertensive patients (7.42 +/- 0.001% and 244 +/- 9.7 mu m respectively, P < 0.001). The media:lumen ratio of both groups examined together correlated with systolic blood pressure (r = 0.45, P < 0.001), diastolic blood pressure (r = 0.56, P < 0.001) and mean arterial pressure (r = 0.55, P < 0.001). The media:lumen ratio of vessels from hypertensive patients correlated with diastolic blood pressure (r = 0.22, P < 0.01) but not with systolic or mean blood pressure. There was no correlation between the media:lumen ratio of small gluteal subcutaneous arteries and pulse pressure in this population of normotensive and hypertensive subjects, examined together or separately. Conclusion These results suggest that in 30- to 65-year-old humans with systolodiastolic essential hypertension, pulse pressure does not appear to be an important determinant of small-artery structure. J Hypertens 1999, 17:381-387 (C) Lippincott Williams & Wilkins.