We compared the overflow of endogenous norepinephrine (NE) upon electrical stimulation, the associated pressor response and rate of initial neuronal uptake of3H-I-NE in the perfused mesenteric arteries of Dahl salt-sensitive (DS) and salt-resistant (DR) rats on two dietary NaCI regimens (0.4 and 8.0% for 2 weeks) from 4 weeks of age. The tissues of two rats, a DS and a DR control, were simultaneously processed and subjected to the same electrical stimulation. The pressor response and overflow of endogenous NE during periarterial nerve stimulation (5, 10 Hz, 1 min) in the tissue of DS rats on a high-salt diet (HS) were significantly greater, while those of DS on a low-salt diet (LS) were moderately but significantly higher than those of DR rats on either a high (HR) or a low-salt diet (LR). The tissue content of NE in DS rats was significantly lower than DR groups. There was a significantly reduced3H-I-NE uptake in the tissues of DS rats on both salt diet groups compared with DR rats. A submaximal dose of exogenous NE evoked a significantly greater pressor response amplitude in mesenteric tissues from DS rats on a high-salt diet than in any of the other three groups, suggesting that smooth muscle supersensitivity, either in the density of the NE receptor or in the excitation-contraction coupling system, had been induced in the vasculature of DS rats by feeding them on a high-salt diet for 2 weeks. These data indicate that enhanced NE overflow and smooth muscle supersensitivity to NE appear to be the most outstanding alterations induced in DS rats fed on a high-salt diet in the initial stages of hypertension