In a randomized placebo-controlled study 12 healthy volunteers were treated for 1 wk each with 10 mg of nifedipine four times daily plus placebo or the same dose of nifedipine concurrently with 40 mg of famotidine once a day. Famotidine did not significantly alter pharmacokinetic parameters of nifedipine. Determination of systolic time intervals showed that the preejection period and the ratio of the preejection period and the left ventricular ejection time were significantly reduced by administration of nifedipine plus placebo. Coadministration of famotidine and nifedipine, however, led to a significant increase of these parameters. In an additional double-blind study, a significant rise of the preejection period and of the ratio was detected after administration of famotidine alone. In impedance cardiography stroke volume and cardiac output were significantly reduced by famotidine. Heart rate and blood pressure values were not altered by the H2-antagonist. For the first time, to our knowledge, the observed changes of hemodynamic parameters appear to indicate that famotidine may exert negative effects on cardiac performance which, in our opinion, could be of clinical relevance in elderly subjects or in patients with heart failure.