Although 5-hydroxytryptamine (5-HT) elicits positive inotropic effects in the human isolated atrium via 5-HT4 receptors, no data are available about its effects in the ventricular myocardium. We investigated the inotropic effects of 5-HT in human healthy ventricular trabeculae and compared these effects with those in right atrial trabeculae. Baseline force of contraction as well as the response to noradrenaline, used to check inotropic responsiveness of the tissue, was significantly higher in ventricular (391 +/- 10 and 719 +/- 126 mg, respectively) than in atrial tissue (189 +/- 5 and 383 +/- 79 mg, respectively). However, 5-HT increased the force of contraction up to 309 +/- 82 mg at 10(-4) M in atrial trabeculae, but failed to affect the force of contraction in ventricular tissue. We conclude that, in contrast to atrial tissue, 5-HT is ineffective as a positive inotropic agent in human ventricular trabeculae. This finding obviously rules out the development of 5-HT4 receptor agonists for the treatment of heart failure, but suggests the absence of ventricular side-effects of 5-HT4 receptor (ant)agonists should these agents be used in the treatment of gastrointestinal disorders.