A non-dialysable substance capable of increasing the permeability of cutaneous capillaries was detected in 25 out of 29 blister fluids, all the 28 plasma samples of patients with vesiculobullous disorders and 19 out of 20 plasma samples of normal controls. This substance was stable at ––10°C for at least 11 days, but was inactivated by heating at 100°C for 1 h. It had no effect on the isolated guinea pig ileum. The activity in the plasma of contact dermatitis patients was statistically higher than the normal con