This was an open, randomized study of the cardiovascular effects of the histamine H2 receptor antagonists ranitidine, famotidine, and nizatidine after single oral doses alone or in combination in healthy volunteers. When compared with placebo ranitidine (450 mg) did not have any haemodynamic effects. Nizatidine (300 mg) caused significant falls in heart rate and cardiac output. Famotidine (40 mg) caused significant falls in stroke volume and cardiac output and an increase in pre-ejection period. Pretreatment with ranitidine abolished the haemodynamic effects of nizatidine and caused a time-shift of 2 h in the onset of the cardiovascular effects of famotidine. The difference in the results for nizatidine and famotidine can be explained by the longer half-life of famotidine. Vascular effects are assumed to be responsible for impairment of cardiac performance by famotidine.