We were able to demonstrate a significant rise of serum digoxin concentrations (SDC) under simultaneous quinidine-glycoside therapy. The reason for this elevation is not yet known. In vitro studies under addition of quinidine showed no influence on the SDC-values measured by a tritium-labelled radioimmunoassay. The mean SDC of 18 patients under simultaneous quinidine therapy was 2.39 +/- 0.84 ng/ml (3.06 +/- 1.08 nmol/l) compared to a mean SDC of 1.23 +/- 0.74 ng/ml (1.57 +/- 0.95 nmol/l) of 11 patients without quinidine therapy (p less than 0.001). Both groups of patients received the same maintenance dose and showed no obvious impairment of renal function and no significant difference in mean body weight. Our results suggest that part of the great number of adverse reactions seen under a combined glycoside-quinidine therapy might be due to the elevated SDC-values. For these patients a low-normal glycoside maintenance dose and an early reduction of the quinidine dose is recommended.