We measured the digoxin concentration in both plasma and erythrocytes in 75 patients by radioimmunoassay during digoxin maintenance therapy. Mean plasma digoxin concentration was 0.90 ng/ml and mean erythrocyte digoxin concentration was 1.44 ng/ml in 75 patients. The ratio of digoxin concentration of erythrocyte to plasma during maintenance therapy was 2.24 in all patients, 1.63 in patients with therapeutic plasma digoxin levels, and 3.52 in patients with subtherapeutic plasma levels. There was a significant correlation between erythrocyte and plasma digoxin concentrations in therapeutic plasma levels (r=0.53, p<0.001). Patients on maintenance digoxin therapy were classified into 6 groups according to plasma and erythrocyte digoxin concentrations; in group I, 7 patients with both low plasma and erythrocyte digoxin concentrations, were poorly controlled in respect to heart failure; in group II, 19 patients with low plasma and medium erythrocyte digoxin concentrations failed to show compliance; in group III also, 3 patients with therapeutic plasma and low erythrocyte digoxin levels showed poor compliance; in group IV, 41 patients with both medium plasma and erythrocyte digoxin levels, were well controlled in respect to heart failure and all were compliant. Careful observation was required to avoid digoxin intoxication in group V with therapeutic plasma and high erythrocyte digoxin concentrations, and in group VI with high plasma and high erythrocyte digoxin concentrations.