Previous studies by our group demonstrated a striking relationship among arginine, nitric oxide production, and salt-sensitive hypertension in the Dahl/Rapp rat. We hypothesized that enzymes of the urea cycle may be involved in this process. We specifically examined the activities of liver and kidney argininosuccinate synthetase (AS), because this enzyme is an essential step of arginine synthesis and a likely control point. We found that salt- sensitive (S) rats on a high-salt diet developed hypertension without change in plasma concentrations of arginine, citrulline, and ornithine. Baseline plasma concentrations of these amino acids were the same in rats of all three genotypes: Sprague-Dawley (SD), S, and salt-resistant (R) Dahl/Rapp rats. In contrast, R rats on the high-salt diet remained normotensive coincidentally with elevated levels of arginine and ornithine, as compared to normotensive R rats on low-salt diet with no changes in amino acid concentrations. S rats on high-salt diet became hypertensive coincidentally with no changes in amino acid concentrations. None of the rat groups had significantly different activity of liver or kidney AS coincidental with the salt in the diet and the changes in amino acid concentrations found in the R rats. Thus, given the lack of alteration in plasma concentrations of the urea cycle amino acids of arginine, citrulline, and ornithine in S rats, genes of the urea cycle/arginine synthesis are unlikely to be involved in salt-sensitive hypertension in this strain. The mechanism of increased plasma arginine and ornithine concentrations in R rats was not determined, but was not related to AS activity.