Elevated serum digoxin concentrations and clinical toxicity have been reported in patients receiving quinidine. The present study was undertaken to ascertain whether a similar interaction occurs between quinidine and another cardiac glycoside, digitoxin, and if so to evaluate the pharmacokinetic basis in five healthy volunteers. In the presence of quinidine the serum digitoxin concentration was elevated, the mean digitoxin elimination half-life was increased from 87.8±11.6 to 218.3±20.6 h (mean ±SEM) (p < 0.01), and mean total body clearance was reduced from 5.01 ± 1.18 to 1.87 ± 0.20 mL/h.kg (p < 0.052). No change was observed in the apparent volume of distribution or in the volume of the central compartment for digitoxin. The data suggest that the mechanism for this interaction is a reduction in elimination and not displacement of digitoxin from tissue binding sites.