Nine patients (median age 78 years, range 62-92) treated with a constant oral dosage of digoxin were evaluated for the effect of trimethoprim on serum digoxin values. Serum digoxin increased by 22% during trimethoprim treatment (p less than 0.05). Subsequently, 6 healthy subjects (median age 29 years, range 24-31) were evaluated for the effect of trimethoprim on digoxin pharmacokinetics after an i.v. dose. Trimethoprim administration did not affect total body clearance of digoxin and the glomerular filtration rate. The renal clearance of digoxin decreased by 17% (p less than 0.05) and the extrarenal clearance of digoxin increased by 14% (N.S.). Biological half-life of digoxin and apparent volumes of central and peripheral compartments were unchanged during the study. It is suggested that the increase in serum digoxin in the elderly patients is due to decreased renal tubular secretion of digoxin and not to disturbance of the extrarenal clearance.