Intact segments of mesenteric resistance arteries (200 µm) from 5-month-old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were tested for norepinephrine (NE) sensitivity. Dose-response curves were obtained both before and after adrenergic denervation produced by short-term, in vitro, 6-hydroxydopamine (6-OHDA) treatment. NE sensitivities of innervated vessels were the same in SHR and WKY rats, however, after 6-OHDA, not only did both ED50s show significant decreases (8.7- and 3.8-fold, respectively), but the ED50 of SHR vessels was half that of WKY (NE sensitivity increased twofold). In addition there was a 33% increase in wall tension generated in response to maximum NE stimulation, and a 44% increase in neuronal NE uptake in the SHR vessels. These results show that several important alterations have occurred in resistance vessels from SHR rats in the established phase of hypertension. The relationship of the increase in neuronal uptake to the increased total peripheral resistance and increased vascular reactivity commonly seen in SHR perfused beds and whole animals is unknown. However, the increases in NE sensitivity and in maximum NE wall tension could contribute to increases in both of these characteristics.