Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large- and medium-size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 +/- 2.9 years, BMI: 22.9 +/- 0.3 kg/m(2), mean +/- s.e.m.) and 17 age-matched severely obese (BMI: 41.1 +/- 2.3 kg/m(2)) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross-sectional area (CSA), and media-to-lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 +/- 0.6 vs. 16.2 +/- 0.6 microm, CSA 22,272 +/- 1,339 vs. 15,183 +/- 1,186 microm(2), and media-to-lumen ratio 0.113 +/- 0.006 vs. 0.059 +/- 0.001, respectively, P < 0.01). Acetylcholine-induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (-40.4 +/- 1.3%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.