The effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pumpα-subunit expression in some tissues of rats were compared. Normal rats were injected with ouabain, digoxin, and normal saline (NS), respectively, everyday, and indirect SBP was recorded once a week. Six weeks later, all the rats were killed, and sodium pump α1-, α2-, and α3-subunit mRNA levels were detected in the myocardium, kidney, adrenal gland, aortic smooth muscle, and hypothalamus by the RT-PCR method. The results showed that the SBP of rats infused with ouabain increased significantly at the end of week 6, while no difference in SBP was found between the digoxin and NS groups. The effects of ouabain and digoxin on sodium pump α-subunit isoform expression were also different. Myocardium: both ouabain and digoxin stimulated expression of the α3-isoform whereas α2 was unchanged. Levels of the α1 isoform decreased significantly in the ouabain group and decreased slightly in the digoxin group, respectively. Kidney: digoxin had the same effects as ouabain. α1 levels increased, but those of α2 and α3 remained unchanged. Adrenal gland: α2 and α3 levels increased, but those of α1 decreased in the ouabain group. α1 and α3 levels increased and those of α2 remained unchanged in the digoxin group. Aortic smooth muscle: both ouabain and digoxin increased α1 and α3 expression. α2 levels decreased in the digoxin group but remained unchanged in the ouabain group. Hypothalamus: both ouabain and digoxin stimulated α1 expression, while α2 and α3 levels remained unchanged. The results of this study have shown that ouabain and digoxin have the different effects on both the systolic blood pressure and expression of sodium pump α-subunit isoforms in some tissues in rats. Further studies on the expression of sodium pump α-subunit isoforms might be helpful for the understanding of the physilolgical role endogenous ouabain and the molecular mechanisms involved in the pathogenesis of hypertension.