We measured the levels of digoxin-like immunoreactivity in the serum of 40 volunteers (20 patients with liver cirrhosis and 20 healthy adults) before and after the administration of a 5-day standard regimen of digoxin. Serum digoxin levels (SDL) were evaluated with two different radioimmunoassay (RIA) kits--Amerlex Digoxin 125I RIA and Digoxin 125I RIA. Digoxin was detectable by each RIA kit in 10 and 15% of controls and 50 and 60% of cirrhotic patients before the administration of the drug, respectively. At the end of the treatment with digoxin, SDL were significantly higher in cirrhotics when compared with those of controls. This study provides evidence that digoxin-like substance(s) is (are) implicated in the detection of high SDL in patients with histologically confirmed liver cirrhosis.