The relationship between aortic metabolism and hypertension was examined in spontaneously hypertensive rats (SHR) and in the normotensive Wistar-Kyoto (WKY) strain of rats. Comparative studies between age-matched animals of both strains showed in the SHR, enhanced activities of the aortic enzymes, iV-acetyl β-glucosaminidase (NAGA) and acid phosphatase, which are associated with lysosomes. Similar increases were shown for aortic 5-nucleotidase activity. Antihypertensive drug treatment of 30-week-old SHR for 17 weeks effectively lowered blood pressure and reduced the activity of aortic NAGA and acid phosphatase in the SHR to control levels. 5′-Nucleotidase activity remained significantly elevated, and aortic collagen and elastin concentrations were unaffected by antihypertensive drug treatment. Hypertension was produced in WKY rats by deoxycorticosterone treatment for either 4 or 7 weeks and then was reversed by discontinuing treatment and maintaining the pretreated animals on a low-salt diet for up to 11 weeks. At the end of the treatment period, aortic enzymatic activity was increased significantly, as were heart and aortic weights. Following the reversal of hypertension, the activity of the lysosomal enzymes was decreased significantly, but 5-nucleotidase activity remained elevated. Collagen and elastin concentrations were not affected by mineralocorticoid treatment, but the total amount of connective tissue protein was increased and remained elevated following the reversal of hypertension, paralleling the changes in aortic weight. The studies indicate that etiologically different forms of hypertension result in characteristic changes in aortic metabolism which are not completely reversed by subsequent blood pressure reduction.