BACKGROUND Intralesionally injected bleomycin is a useful agent for the treatment of recalcitrant warts. The mechanism of action in wart therapy has been thought to be due to DNA and antiviral effects. To further characterize the inflammatory response to intralesional bleomycin injections, we examined the clinical, histologic, and immunopathologic response to intradermal bleomycin injections in normal human skin. RESULTS Four volunteers were each given four intradermal bleomycin injections (0.01 to 0.5 U/mL) into normal human skin to establish a dose response. These injections induced a localized time and dose-dependent inflammatory reaction and persistent postinflammatory hyperpigmentation. Nine biopsy specimens from two volunteers were taken at different time points after intradermal bleomycin injections (0.1 to 1.0 U/mL) into normal human skin. Routine histologic study demonstrated dyskeratosis and necrosis of epidermal keratinocytes and eccrine epithelium associated with a prominent neutrophilic infiltrate, closely resembling histopathologic findings seen in neutrophilic eccrine hidradenitis. Expression of HLA-DR and intercellular adhesion molecule 1 was induced on keratinocytes; intercellular adhesion molecule 1 was upregulated, and endothelial leukocyte adhesion molecule 1 was induced on superficial dermal blood vessels. CONCLUSIONS These findings suggest that intradermal bleomycin injection is either directly or indirectly cytotoxic to keratinocytes and eccrine epithelium. Expression and upregulation of activation antigens and cell adhesion molecules suggest that a cellular immune system response and proinflammatory cytokine secretion occur after intralesional bleomycin injection into normal human skin. Histopathologic findings at some injection sites resemble neutrophilic eccrine hidradenitis.