Objective: Ion channels, which are responsible for the controlled functioning of many cell biological processes, are present on the cell membrane of all living human cell systems under physiological conditions. A relationship between ion channel activity and proliferation behaviour has been demonstrated in various cell systems. The aim of the paper is to prove to what extent the proliferation, CD44 expression and the apoptosis behavior of cells can be influenced by the modulation of ion channel activity on the cell membrane of human osteoarthritic chondrocytes. Material and Methods: Human chondrocytes were isolated from osteoarthritic knee joint cartilage. The culture was made as a monolayer in RPMI medium with addition of 10% fetal calf serum, 50 µg/mL gentamycinsulfate and 2 µg/mL Amphotericin B at 37°C and 5% carbon dioxide. The voltage dependent Na+ channel blocker lidocaine, the calcium antagonist verapamil, the K+ channel blocker 4-Aminopyridine (4-AP) and the chloride and anion channel blocker 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS) were used as ion channel modulators. Proliferation was determined using ³H-thymidine incorporation as the measure. Proof of the CD44 membrane protein was performed by flow cytometry with an FITC-conjugated CD44 antibody (anti-CD44H-FITC). For apoptosis detection, the translocation of phosphatidylserine (Annexin V-FITC Assay), determination of Apo2.7 and the Caspase activity on cytokeratin 18 were determined by flow cytometry. Results: The results show that proliferation behavior can be regulated by all four ion channel modulators, whereby lidocaine, 4-AP and SITS result in a transient increase in ³H-thymidine incorporation. All substances resulted in marked suppression of proliferation after longer incubation times. At the same time, no influence of lidocaine could be determined on the apoptosis of human chondrocytes, whereas marked cytotoxic effects occurred under verapamil and 4-AP. SITS leads to necrotic cell damage. CD44 expression is increased the incubation with lidocaine or 4-AP for 24 h or 48 h, whereas prolonged incubation under SITS or verapamil influence leads to a clear inhibition of CD44- expression. Conclusion: Proliferation, CD44- expression and apoptosis behavior of human chondrocytes can be influenced by modulation of ion channel activity. These results serve as a basis for further investigations to extend therapeutic possibilities in the treatment of arthritis.