Serotonin 5-HT(4) receptors are present in human atrial myocytes and have been proposed to contribute to the generation of atrial fibrillation (AF). Here, we quantified 5-HT(4) receptors as well as other key genes involved in cardiac rhythm and contraction in right atrial appendages of patients with chronic AF (CAF) and acute AF (AAF). Right atrial appendages were obtained from eleven patients in sinus rhythm (SR), five with AAF and six with CAF (>12 months). TaqMan real time quantitative RT-PCR was performed on total RNA. Results were normalised to the average of three housekeeping genes, cyclophilin, GADPH and RL-19. The rank order of expression of h5-HT(4) receptors variants was (b)>(a)>(g)>(c) in the group of patients in SR. In AAF, we found a strong decrease in h5-HT(4(b)), h5-HT(4(c),) and h5-HT(4(g)) transcripts. In CAF patients, the mRNA expression level of the h5-HT(4(b)) isoform significantly increased two fold versus SR. A similar increase was reported for beta(1)-adrenergic receptor, connexin 43 and the L-type Ca(2+) channel CaCNA1C subunit. Interestingly, CAF was associated with a strong increase in the expression of Na(+)/Ca(2+) exchanger and the voltage-dependent Na(+) channel SCN5A subunit. Our results indicate that h5-HT(4(b)) is the dominant cardiac isoform of human 5-HT(4) receptors and its expression is increased in CAF. These data support the involvement of 5-HT(4) receptors in atrial arrhythmia.