Since adrenal steroids have been shown to upregulate the concentration of Na+-K+-ATPase in cardiac muscle, similar effects could be expected in skeletal muscle. Following infusion of dexamethasone (0.02-0.1 mg/kg per day) for 7 days in 10-week-old rats, the total concentration of [H-3]ouabain-binding sites rose by up to 22-42% in soleus, extensor digitorum longus, gastrocnemius and diaphragm muscle. Dexamethasone produced no or minute changes in the Na+-K+ contents of skeletal muscle. In contrast, infusion with aldosterone (0.02-0.5 mg/kg per day) for 7 days produced hypokalemia and a graded reduction in the K+ content of skeletal muscle, which was closely correlated to a downregulation of the [H-3]ouabain-binding site concentration (r = 0.65-0.70; P<0.001). The results indicate that in skeletal muscle high doses of glucocorticoids upregulate the concentration of Na+-K+ pumps whereas mineralocorticoids induce a downregulation, which is secondary to the concomitant K+ deficiency. Since adrenalectomy produced no significant change in [H-3]ouabain-binding site concentration, basal levels of endogenous adrenal steroids seem to be of minor importance for the regulation of Na+-K+ pump concentration in skeletal muscle.