The digoxin content was measured in samples of left ventricular papillary muscle, skeletal muscle, and plasma obtained during mitral valve replacement from eight patients on maintenance treatment with the drug. The content in papillary muscle ranged from 15.5 to 132 ng/g (mean 77.7) and in skeletal muscle from 7.5 to 23 ng/g (mean 11.3). The ratio of myocardial digoxin concentration to plasma concentration varied between patients from 39:1 to 155:1. No simple relationship exists between plasma levels of digoxin and its concentration in the heart muscle, but total myocardial concentration may not accurately reflect therapeutic activity.