The secretion of the Panton-Valentine leukocidin (Luk-PV) but not of another leukocidin (Luk-R) from Staphylococcus aureus strains is correlated with severe pyodermic infections (dermonecrosis). The effects of both Luk-PV and Luk-R in amounts of 0–5000 ng on inflammatory mediator release from human leukocytes were studied. Luk-PV but not Luk-R induced a pronounced release of the vasodilator histamine from human basophilic granulocytes (up to 55% ± 7%) and of enzymes (β-glucuronidase, up to 45% ± 10%; lysozyme, up to 35% ± 7%), chemotactic components leukotriene B₄ (42 ± 8 ng/107 cells) and interleukin-8 (up to 33 ± 5 ng/10⁷ cells), and oxygen metabolites from human neutrophilic granulocytes. The results indicate that granulocytes playa central role in dermonecrosis; these in vitro data account for the histologic picture of Luk-PV infections, characterized by local vasodilation, infiltration of granulocytes, and a central necrotic area.