An open randomized crossover trial to investigate quinidine-digoxin interactions under steady-state conditions with special attention to quinidine pharmacokinetics was performed in 6 healthy male volunteers. Coadministration of quinidine sulphate induces a prolongation of digoxin elimination half-life (means +/- SD) from 33.0 +/- 8.0 to 43.9 +/- 6.2 hours, causing an augmentation of 0/48 AUC (means +/- SD) from 37.8 +/- 14.1 to 100.2 +/- 30.4 ng/ml.h. This increase in serum digoxin concentration-time course was caused by a decrease of both renal clearance (means +/- SD) from 150.7 +/- 46.5 to 79.0 +/- 23.3 ml/min and of minor importance, total clearance (means +/- SD) from 198.8 +/- 66.4 to 91.7 +/- 21.9 ml/min. A decrease in apparent volume of distribution of digoxin (means +/- SD) from 520.1 +/- 115.2 to 344.5 +/- 78.2 l could also be observed: When digoxin was given additionally, two quinidine-pharmacokinetic parameters were altered: renal quinidine clearance decreased from (means +/- s) 61.2 +/- 11.5 to 45.7 +/- 13.7 ml/min, causing a prolongation of elimination half-life of quinidine (means +/- s) from 10.34 +/- 1.76 to 12.28 +/- 1.23 hours. These altered parameters induced an augmentation in 0/48 AUC of quinidine of 11% on the average but this change was not statistically significant because of the relatively large standard-deviation in serum quinidine concentrations. Considering the reduction of renal digoxin clearance, the mechanism mainly responsible for the quinidine-digoxin interaction, the decrease in renal quinidine clearance, appears to be most remarkable as well.