The association between uterine smooth muscle fibroids and systemic arterial hypertension is poorly understood. Therefore, we explored possible concomitant myocyte pathology of systemic resistance-sized arterioles (200 to 400 μm), isolated from omental samples donated by 19 women (mean age 42 y; SE 1) undergoing fibroid surgery. Vessels of 17 women (8 hypertensives) were available for transmission electron microscopy. We found ultrastructural vessel wall abnormalities in all patients, albeit with greater severity in hypertensives. In the endothelium, this ranged from moderate mitochondrial and endoplasmic reticulum stress in normotensives, to necrosis and sloughing in hypertensives. Myocyte-like cells were observed to migrate across the internal elastic lamina, with isolated subendothelial myocytes in normotensives, and focal subendothelial multicellular aggregates or myo-intimal "cushions" in hypertensives. Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria, and myofilament loss involving focal areas or entire cells. To our knowledge, the first study on the ultrastructure of systemic resistance arterioles of women with fibroids indicates that severe abnormalities are present that likely affect blood pressure regulation. Whether these perturbations are induced by fibroids, or represent systemic pathology that affects myocytes of both uterine and vascular tissue warrants further exploration.