The pathogenesis of venous leg ulcers is based on the leakage of fibrinogen leading to pericapillary fibrin cuff and plugging of capillaries by white blood cells. Eight patients with venous leg ulcers have been studied with a panel of antibodies reactive for fibrinogen, fibrin, fibrin degradation products, and various cell-associated markers for polymorphonuclear cells, monocytes, and B and T lymphocytes. Our results showed that pericapillary fibrin cuff was mainly composed of undegraded fibrin and that, in the granulation tissue, tumor necrosis factor-α and elastase activities were detectable in monocytes and polymorphonuclear cells, respectively. Only few activated lymphocytes were present. On the basis of these results, it is assumed that inflammation generated by activated white blood cells that accumulate under unrelieved pressure is the key event. Tumor necrosis factor—α synthesized by activated monocytes may therefore induce the formation of pericapillary fibrin cuffs. Pericapillary fibrin cuffs and toxic metabolites released by polymorphonuclear cells may explain the absence of wound repair.