The effects of hyperkalemia on serum and myocardial digoxin (DX) concentration was studied in conjunction with hemodynamic changes in 31 normal dogs. The myocardial DX concentration in the hyperkalemic (HK) group was significantly lower than that in normokalemic (NK) group, despite a significantly higher serum DX concentration in the HK group. In the HK group, the myocardial sodium concentration was significantly lower than in the NK group. Coincident with these biochemical changes, no increase of LV max dP/dt after DX administration was observed in the HK group. These results suggest that there might be competitive antagonism between myocardial uptake of potassium and DX.