Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT₁) and type 2 (AT₂) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT₁ and AT₂ receptors. Immunoreactivity to AT₁ and AT₂ was localized to stratum superficiale and spinosum in the epithelium. ACE, AT₁, and AT₂ were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT₁ receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was −6.4 mV, epithelial current (I_ep) 34 μA/cm², and epithelial resistance (R_ep) 321 Ω·cm². Serosal exposure to Ang II increased PD as a result of increased I_ep, whereas R_ep was constant. Ang II given together with the selective AT₁-receptor antagonist losartan, or AT₂ agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT₂-receptor antagonist PD123319 did not influence PD, but I_ep decreased and R_ep increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT₂-receptor stimulation increases epithelial ion transport, whereas the AT₁ receptor inhibits ion transport and increases R_ep.