Members of the transient receptor potential (TRP) family are temperature sensors, and TRPV1, V3, and V4 are expressed in epidermal keratinocytes. To evaluate the influence of these receptors on epidermal permeability barrier homeostasis, we kept both hairless mouse skin and human skin at various temperatures immediately after tape stripping. At temperatures from 36 to 40 degrees C, barrier recovery was accelerated in both cases compared with the area at 34 degrees C. At 34 or 42 degrees C, barrier recovery was delayed compared with the un-occluded area. 4Alpha-phorbol 12,13-didecanone, an activator of TRPV4, accelerated barrier recovery, whereas ruthenium red, a blocker of TRPV4, delayed barrier recovery. Capsaicin, an activator of TRPV1, delayed barrier recovery, whereas capsazepin, an antagonist of TRPV1, blocked this delay. 2-Aminoethoxydiphenyl borate and camphor, TRPV3 activators, did not affect the barrier recovery rate. As TRPV4 is activated at about 35 degrees C and above, whereas TRPV1 is activated at about 42 degrees C and above, these results suggest that both TRPV1 and TRPV4 play important roles in skin permeability barrier homeostasis. Previous reports suggest the existence of a water flux sensor in the epidermis, and as TRPV4 is known to be activated by osmotic pressure, our results indicate that it might be this sensor.