Immune dysfunction has been reported in patients with hypertension and in spontaneously hypertensive rats. Increased circulating levels of ouabain were observed in experimental models and in human hypertension. Despite the correlation between immunologic depression and hypertension, the mechanisms involved are unclear. This review examines evidences of immune dysfunction in hypertension and presents observations suggesting that ouabain is capable of inducing lymphocyte changes related to some of the immune disturbances observed. Defects in thymocytes, mature lymphocyte subsets, lymphocyte proliferation, cytokines balance and increased immunoglobulin production, were reported in animal models and/or hypertensive patients. Ouabain potentiates the effects of glucocorticoids on thymocytes, inducing plasma membrane depolarization, loss of mitochondrial membrane potential, changes in CD69 levels, increased intracellular calcium and apoptosis of thymocyte subsets. The activation of mature lymphocytes is inhibited by ouabain following different stimuli and these cells display changes in c-myc, CD69 and CD25 levels, plasma membrane polarization and mitochondrial membrane potential. These cells underwent apoptosis, suggesting an exacerbation of the process of activation induced cell death. Levels of cytokines such as IL-1, IL-2, IL-6, TNF, and GM-CSF are modified by ouabain. Some of the ouabain effects may result from a mechanism different from the traditional inhibition of the Na+/K+ ATPase.