Simultaneous administration of cimetidine and nifedipine to six healthy volunteers produced an about 80% rise in maximal plasma levels and the area under the plasma level-time curve of nifedipine compared with results on nifedipine administration alone (P less than 0.05). After treatment for one week with 4 X 10 mg nifedipine daily and 3 X 200 mg cimetidine daily and 400 mg at night plasma level peaks of nifedipine averaged 87.7 +/- 19.1 ng/ml, while after 4 X 10 mg nifedipine alone they were only 46.1 +/- 10.6 ng/ml. Ranitidine produced an approximately 25%, nonsignificant, rise in plasma level-time curve and peak plasma levels of nifedipine. Seven hypertensives (WHO stage I and II) had a mean arterial blood pressure level of 127 +/- 2.5 mm Hg after two-week placebo administration, and of 109 +/- 2.38 mm Hg after four weeks of nifedipine alone at 4 X 10 mg daily (P less than 0.01). After additional administration of 1 g cimetidine daily for two weeks the mean blood pressure fell significantly to 95 +/- 3.1 mm Hg (P = 0.02), while blood pressure fell to 103 +/- 3.88 mm Hg after two weeks of additional administration of 300 mg ranitidine daily, a fall which was not significant (P greater than 0.05). The interaction of nifedipine and cimetidine is thus of clinical significance because of its pharmacodynamic effect.