Blister fluids from 39 previously untreated patients with pemphigus vulgaris (PV) and 28 patients with bullous pemphigoid (BP) were tested for the presence of inflammatory mediators. Blister fluids from patients with PV and BP showed interleukin 1 (IL-1)- and interleukin 2 (IL-2)-like activity and contained prostaglandin (PG) E2, F1 alpha, and F2 alpha, thromboxane B2 (TB2), leukotriene (LT) B4 and C4, serine esterases, and proteolysis inhibitors. Pemphigus blister fluid was distinguished by high IL-1-like activity, proteolytic activity, and high concentrations of TB2 and LTB4, while pemphigoid blister fluid was characterized by higher IL-2-like activity, antiprotease activity, and high PGE2 concentration. We also determined that the content of mediators of inflammation varied depending on the duration of blister development. In both PV and BP, the initially high IL-1-like activity, amount of serine proteases, and concentrations of PGF2 alpha, TB2, LTB4, and LTC4 decreased by the fifth day of blister existence, whereas antiprotease activity as well as PGE2 and PGF1 alpha concentrations gradually increased as blisters developed. These findings suggest certain differences in the character of the bullous inflammatory process in pemphigus and pemphigoid.