In this study, the lymphocytes and erythrocytes from peripheral venous blood were used as the study model from which were measured the cellular contents of potassium, sodium, calcium and magnesium in 50 patients with chronic congestive heart failure and 39 control patients. Levels of endogenous digoxin-like substance in the plasma and activities of Na/K ATPase in red cell membrane wer monitored simultaneously. In the patients with heart failure, the intracellular contents of potassium and magnesium were decreased while those of sodium and calcium were increased significantly. The levels of endogenous digoxin-like substance were much higher in the plasma than those either in healthy controls or in patients with heart disease but without congestive failure (273.7 +/- 35.5 vs 23.3 +/- 2.2 and vs 32.9 +/- 3.6 pg/ml, respectively, P less than 0.001 for both). The activities of Na/K-ATPase were much lower in the patients with heart failure than in the controls. Values for intracellular electrolytes were significantly correlated with the rising levels of digoxin-like substance in the plasma. Non-digitalis inotropic therapy was associated with the recovery of these alterations of heart function, with the levels of the digoxin-like substance decreasing and activity of Na/K-ATPase going up. We conclude that endogenous digoxin-like substance might play a role in the imbalance of intra-cellular electrolytes seen in patients with congestive heart failure. Digoxin may exacerbate the loss of intracellular potassium.