To assess the possible contribution of brain ouabain-like activity (OLA) to the pressor effects of high-sodium intake in Dahl salt-sensitive (Dahl S) rats, we assessed the effects of high (8%) on blood pressure (BP) and peripheral and brain OLA in Dahl on blood pressure (BP) and peripheral and brain OLA in Dahl S and Dahl salt-resistant (Dahl R) rats. On regular sodium intake, Dahl S and R had similar BP; however, by 7 wk of age adrenal and plasma OLA were 15-30% higher in Dahl S vs. R, whereas central OLA remained similar. On high-sodium intake, in Dahl S both peripheral and central OLA increased within 1 wk with additional increases after 3 wk. These increases preceded the rise in BP. In Dahl R rats, high sodium did not increase BP. However, 3 wk of high sodium did increase peripheral as well as central OLA, the latter to a lesser extent compared with Dahl S and not in the hypothalamus. These results are consistent with the concept that central OLA may be involved in the pressor responses to high sodium in Dahl S. Circulating OLA may play a role in the regulation of renal function to excrete excess sodium in both strains.