Bed bugs may cause mild to severe cutaneous reactions. We studied the ability of bed bug salivary extract (SGE) to induce inflammatory reactions responsible for cutaneous manifestations and found that SGE stimulated the production of several potent chemokines and cytokines from macrophages. Chemokines induced by SGE included those known to recruit eosinophils (eotaxin), attract neutrophils [interleukin (IL)-8] or induce their survival and proliferation (granulocyte colony-stimulating factor). Cytokines involved in cell-mediated immunity, including IL-7, IL-10 and IL-12, were also induced. Saliva of bed bugs contains protein and non-protein molecules that have pleotropic effects on macrophages, orchestrating the immune response in the skin after bed bug bites.