Strophanthidin, a cardiac aglycone, interferes with Na+, K+ and H+ ion transport by the renal tubule cells of the chicken. Injection of 250–500 µg/min. of the aglycone into the renal-portal circulation results in a predominantly unilateral increase in Na+ excretion and alkalinization of the urine. K+ excretion diminishes if initially elevated by prior administration of KCl or K2SO4. The concordant changes in K+ and H+ ion secretion associated with depressed reabsorption of Na+ are in contrast to reciprocal alterations in K+ and H+ ion transport observed with carbonic anhydrase inhibitors. The data have been interpreted as indicating that the aglycone inhibits a contraluminal Na+, K+ exchange pump (analogous to that in other tissues) and that the urinary changes are secondary to this and not a consequence of a primary reduction in the capacity of a linked Na+, K+, H+ ion exchanger on the luminal border.