The effects of 5-carboxamidotryptamine (5-CT) and the gastrokinetic benzamides renzapride and cisapride on contractile force were investigated using isolated paced right atrial appendages from patients treated with beta-adrenoceptor blocking agents who were undergoing open heart surgery. These effects were compared to those of 5-hydroxytryptamine (5-HT). The effects of the drugs on atrial cyclic AMP levels and cyclic AMP-dependent protein kinase ratios were also investigated. The drugs all increased contractile force of rank order of potency was 5-HT greater than renzapride greater than cisapride greater than 5-CT. The maximum responses, expressed as a fraction of the response to 200 mumol/l (-)-isoprenaline, were 5-HT 0.6, 5-CT 0.6, renzapride 0.4 and cisapride greater than or equal to 0.2, suggesting that the latter two are partial agonists. 5-HT, 5-CT and renzapride but not cisapride caused significant shortening of time to peak force. The effects of the four drugs were blocked by mumolar concentrations of ICS 205-930, suggesting an involvement of 5-HT4 receptors. As expected of partial agonists both renzapride and cisapride caused simple competitive antagonism of the positive inotropic effects of 5-HT. The estimated equilibrium dissociation constants pKP (-log mol/l KP) were 6.7 for renzapride and 6.2 for cisapride. 5-CT at concentrations up to 10 mumol/l did not antagonise the effects of 5-HT. In the presence of (+/-)-propranolol 0.4 mumol/l, 5-HT 10 mumol/l, 5-CT 100 mumol/l, renzapride 10 mumol/l and cisapride 40 mumol/l significantly increased cyclic AMP levels. 5-HT and renzapride also significantly increased cyclic AMP-dependent protein kinase activity, whereas 5-CT caused only marginal stimulation and cisapride was ineffective. The results confirm the existence of a human right atrial 5-HT receptor that is similar in nature to, but not necessarily identical with, the 5-HT4 receptor of mouse embryonic colliculi neurones. The main difference is that in human right atrium the benzamides are less potent and efficacious than 5-HT and that cisapride is less potent and less efficacious than renzapride while in mouse embryonic colliculi these two benzamides are equipotent with and more efficacious agonists than 5-HT. We designate the human right atrial 5-HT receptor 5-HT4-like. The human right atrial 5-HT4-like receptor greatly resembles porcine sinoatrial and left atrial 5-HT4-like receptors and also appears to be similar to 5-HT4-like receptors of guinea-pig ileum and rat oesophagus.