We investigated the regulation of the protein expression of the α isozymes of Na + ,K + -ATPase in reference to the enzyme activity in the heart, brain and skeletal muscle of rats during deoxycorticosterone acetate (DOCA)-salt hypertension. Treatment of rats with DOCA and salt for 28 days produced a significant increase in systolic blood pressure compared to the control groups which remained normotensive. Rats treated with DOCA expressed greater amounts of the immunoreactive α-1 isoform than untreated controls in whole heart membranes. However, the DOCA-induced increase in the α-1 isoform did not occur during DOCA-salt hypertension. There was a parallel change in the enzyme activity of the Na + ,K + -ATPase and the protein expression of the α-1 isoform as a result of these treatments. We have also demonstrated that the hearts of DOCA-salt hypertensive rats expressed less of the α-2 isoform compared to the controls. We could not detect any alteration in the α-1 and α-2 isoforms of the skeletal muscle and α-1, α-2 and α-3 isoforms of the whole brain Na + ,K + -ATPase during salt or DOCA treatments alone or DOCA-salt hypertension. Furthermore, the Na + ,K + -ATPase activity was unaltered in these tissues during these treatments. In conclusion, cardiac Na + ,K + -ATPase α-subunit protein expression appears to be regulated during DOCA-salt hypertension. In the skeletal muscle and brain, tissues not subjected directly to increased pressure, this regulation of the Na + ,K + -ATPase was not apparent.