The dose-dependence of the nifedipine-digoxin interaction was investigated in seven healthy subjects. After an adequate loading dose of digoxin for 2 weeks, 0.25 mg digoxin b.i.d. was given by mouth by itself. Afterwards, 0.25 mg digoxin was given twice a day for three 1-week periods in combination with capsules of nifedipine, 5, 10, or 20 mg, respectively, given on a thrice-daily basis. The study ended with a digoxin monotherapy phase lasting 7 days. All three doses of nifedipine significantly increased digoxin plasma concentrations and AUC compared with digoxin monotherapy. Thus, for example, the AUC was 10.16 +/- 0.88 ng/ml . hr (mean +/- SE) when digoxin was given alone and 12.33 +/- 1.59 ng/ml . hr with concurrent nifedipine, 5 mg t.i.d. (P less than 0.05). Nifedipine causes a slight but significant increase (15%) in digoxin plasma concentrations and AUC. This effect did not depend on the nifedipine dose given in the range studied.