WAS-deficient myeloid cells drive excess inflammation. In response to infectious or other stimuli, the inflammasome is activated in macrophages, triggering elaboration of IL-1β, IL-18, and other cytokines. Patients with WAS have an excess of proinflammatory M1 macrophages, and M2 macrophages inappropriately secrete IL-1β. The regulatory cytokine IL-10 requires WASP to signal in macrophages, which results in failure to differentiate into M2 macrophages, an important source of IL-10. Plasmacytoid dendritic cells in patients with WAS are poor producers of type 1 interferon. The lack of type 1 interferons fuels macrophage activation directly by failing to turn off the inflammasome and indirectly by insufficient activation of CD8 T cells needed to clear the original infectious trigger. Professional illustration by Patrick Lane, ScEYEnce Studios.