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Introduction: The absorption of water and ions is an important function of colonic epithelial cells. Despite the comprehensive animal studies, there are only scarce data on the ion transporter activities of the normal and inflamed human colon. The aim of our study was to determine the expressional and functional characteristics of Na+/H+ exchangers (NHE) 1–3 and Cl-/HCO3- exchangers (AE) in primary colonic crypts in control patients and in patients with ulcerative colitis (UC). Methods: Colonic biopsies were obtained from normal and inflamed mucosa of patients undergoing colonoscopy. After collagenase digestion, the isolated colonic crypts were loaded with the pH sensitive fluorescent dye BCECF. Intracellular pH (pHi) was measured by microspectrofluorimetry. The mRNA expression of NHEs and the SLC26A3 Cl-/HCO3- exchangers (DRA) was assessed by real-time PCR. Results: The activities of NHE1 and 3 isoforms showed a decreasing pattern from the proximal to the distal part of the colon, whereas AE activity was significantly higher in the distal vs. the proximal part of the colon. Only the mRNA expression of NHE3 was decreased in the distal part of the colon vs. the proximal part. No significant difference was detected between the mRNA expression of DRA at the distal and proximal parts of the large intestine. The activity of NHE1 was significantly higher and the activity of NHE3 was significantly lower in UC vs. control. Decreased AE activities were detected in patients with UC compared with the controls. Significant upregulation in the mRNA levels of NHE1 was revealed in UC; however, no significant changes were detected in the mRNA expression of NHE3 in UC. mRNA levels of DRA were reduced by approximately 50% in UC patients compared to non-inflamed controls. Conclusions: Both the absorptive and secretory functions of the colonic ion transporters are altered in UC, which may have roles not only in development of diarrhea but also in the disease activity. This work was supported by OTKA, MTA and NKTH.