The influence of capsaicin processing on human intestinal cell line Caco-2 was examined by measuring transepithelial electrical resistance (TER). There was an increase in permeability at high concentration (200 to 500 muM) of capsaicin, and the effect was inhibited by pretreatment of capsazepine, which is a competitive antagonist of the vanilloid receptor 1 (VR1). LDH-activity as well as changes in intracellular Ca(2+) were determined to know whether or not capsaicin affected TER activity through its influence on the tight junction. We also determined the expression of the VR1-like protein on Caco-2 cells in time-dependent manner by western blotting using vanilloid receptor (VR1) antiserum. Our results showed that the permeability increase by capsaicin was through binding to VR1-like protein of Caco-2 cells.