Digoxin concentration of 14 left ventricular papillary muscles and 36 right atrial appendages of 45 patients undergoing cardiac surgery were determined by the NEN 125J-radioimmunoassay. Blood specimens for digoxin assay were withdrawn immediately before operation, 12 to 16 hr after the last digitalis dose. Mean papillary muscle digoxin concentration was 76.1 ng/g +/- 25.5; mean ratio to plasma digoxin level, 36.8:1. The mean concentration of right atrial appendages was 41.8 ng/g; mean ratio, 29.9:1. Most of the tissue specimens were examined histologically using Hematoxylin-Eosin and van Gieson stains. No clear relation between tissue digoxin concentration and hisological alteration, i.e., the degree of fibrosis or lipomatosis, could be found, although most severe alterations were found in right atrial appendages corresponding to a higher variation in tissue concentrations and a poorer correlation to plasma digoxin (r = 0.47, respectively for papillary muscle r = 0.73).