Plasma myocardial, and skeletal muscle digoxin concentrations were measured in 32 patients undergoing cardiopulmonary bypass who were on long-term treatment with digoxin. The patients were divided into 4 groups according to the daily digoxin dose and the interval between discontinuation of the drug and operation. Before bypass, the mean digoxin concentrations were 1.58 nmol/l (1.24 ng/ml) in plasma 65.2 nmol/kg (50.9 ng/g) in the atria, 121.4 nmol/kg (94.98 ng/g) in 11 papillary muscles, and 16.6 nmol/kg (13.0 ng/g) in skeletal muscle. Mean atrial digoxin concentrations were significantly lower tham mean papillary muscle concentrations in 11 patients. Ratios of plasma of myocardial or skeletal muscle digoxin concentrations were very variable. Generally digoxin concentrations were higher in patients on the larger digoxin dose and with the shorter discontinuation time before surgery. These differences attained significance only with plasma digoxin concentrations. There was a slight fall in plasma digoxin concentration during cardiopulmonary bypass but no significant differences were observed between plasma, atrial, or skeletal muscle digoxin concentrations before and at the end of bypass. No clear relation was seen between plasma or atrial digoxin concentrations and postoperative cardiotoxicity. Stopping digoxin 48 hours before operation appeared to account for pre- or post-bypass plasma digoxin concentrations of less than 1.0 nmol/l (0.8 ng/ml) in most of the instances encountered, whereas the 3 patients who developed pulsus bigeminus postoperatively had received 0.5 mg digoxin only 24 hours before operation.