Current concepts of the pathophysiology of necrotizing fasciitis (NF), a life-threatening infection of soft tissues associated with a toxic shock syndrome, emphasizes the role of bacterial superantigens as mediators of cytokine release by immune lymphocytes. In order to assess the cellular basis of immune activation, immunohistochemistry was applied to the analysis of inflammatory cell subsets in situ in 13 patients with NF. The percentage of inflammatory cells in skin and soft tissue was scored from 0 to 3+ (>50%). Substantial numbers of CD15+ polymorphonuclear leukocytes were present in 12 of 13 patients. CD3+ T-lymphocytes accounted for >10%, CD68+ macrophages for >50%, and Factor XIIIa+ mononuclear cells for >10% of the mononuclear cell infiltrates, respectively, in 10 of 13 patients, whereas CD1a+ cells were present in only 3 of 13 cases and accounted for <10% of mononuclear inflammatory cells. We conclude that immune lymphocytes and accessory immune cells are represented in substantial numbers in the early lesions of NF, and their presence supports current concepts with respect to the pathophysiology of this disorder.