How neutrophils (polymorphonuclear neutrophils, PMNs) damage vessels in leukocytoclastic vasculitis (LcV) mediated by immune complexes (ICs) is unclear. If degradative enzymes and oxygen radicals are released from PMNs while adhering to the inner side of the vessel wall, they could be washed away by the blood stream or neutralized by serum protease inhibitors. We investigated if in LcV PMNs could damage vessels from the tissue side after transmigration. We used CD18-deficient (CD18-/-) mice because the absence of CD18 excludes transmigration of PMNs. When eliciting the Arthus reaction in ears of CD18-/- mice, deposition of ICs was not sufficient to recruit PMNs or to induce IC-mediated LcV. Injection of PMNs intradermally in CD18-/- mice allowed us to investigate if bypassing diapedesis and placing PMNs exclusively on the abluminal side leads to vascular destruction. We found that injected PMNs gathered around perivascular ICs, but did not cause vessel damage. Only intravenous injection of wild-type PMNs could re-establish the Arthus reaction in CD18-/- mice. Thus, PMNs cause vessel damage during diapedesis from the luminal side, but not from the perivascular space. We suggest that in order to shield the cytotoxic products from the blood stream, ICs induce particularly tight interactions between them, PMNs and endothelial cells.