Studies were made on io8 subjects on routine oral maintenance digoxin therapy. Twenty-two were found to have eidene of digoxin toxicity. The range of plasma digoxin concentrations in these subjects is recorded (1.38 SD+oO77 ng/ml). The subjects with evidence of toxicity are shown to have significantly higher plasma digoxin concentrations (3.36 SD I2o ng/ml) though there is some overlap with the non-toxic group. The subjects with toxicity are shown to be substantially older and to have a much higher incidence of raised blood urea. The implications of these observations are discussed.

Summary: A rapid, sensitive, and precise method for measuring the plasma digoxin concentration has been developed with the radioimmunoassav technique. Seventy patients receiving digoxin were shown to have plasma digoxin concentrations between 0.4 and 5 ng./ml. Preliminary studies show that though there is a positive correlation between total daily dose and the plasma digoxin concentration, the relationship is not close, and a relatively wide range of plasma digoxin concentrations appear to be consistent with effective digitalization.

1 Four healthy persons and ten patients with heart failure were studied for 5 to 20 days after they started taking digoxin. The sodium content of their erythrocytes increased and there was an equimolar decrease in potassium content. 2 The increase in erythrocyte sodium for a given increase in plasma digoxin during this acute digitalization was less on average and varied more in the patients than in the healthy persons, that is the patients' erythrocytes were less responsive to digoxin. 3 The average erythrocyte sodium was greater in 183 patients who had been taking digoxin for at least 2 months than in 100 healthy persons not taking digoxin but there was no significant correlation between the plasma digoxin concentrations and erythrocyte sodium concentration in the patients. Indeed, there was no apparent change in the erythrocyte sodium in many of the patients taking digoxin. 4 If the erythrocyte sodium concentration is a reliable guide to the tissue effects of digoxin then the results suggest that there is a wide variation in the response to digoxin between patients both during acute digitalization and during chronic treatment with digoxin.

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