Basophils and eosinophils are important effector cells in human allergic diseases; they play a significant role in promoting allergic inflammation through the release of proinflammatory mediators (such as histamine, leukotriene C(4), major basic protein, eosinophil cationic protein, IL-4, and IL-13, among others). Notably, in allergic subjects, these cells exist in higher numbers and in a more activated state compared with nonatopic control subjects. Evidence for the greater activation state includes increased expression of intracellular and surface markers and hyperreleasability of allergy mediators. We have been interested in the phenotypic markers of effector-cell activation for many years. There is considerable overlap among activation markers, and few activation markers have been found that define a unique phenotype that is quantifiable in the assessment of the presence and severity of allergic disease. This review summarizes the existing evidence for systemic activation of human basophils and eosinophils in allergic diseases. The potential mechanisms responsible for functional and morphologic alterations in these effector cells and the specificity and utility of surface markers in the assessment of allergic disease activity or severity are also discussed.