The mechanisms that could affect the lifespan of eosinophils after they have left the bone marrow, and their capacity to respond to activation factors were studied by examining the effects of IL-5, GM-CSF and IL-3 on purified human blood eosinophils in culture. All three cytokines prolonged the lifespan of the majority of blood eosinophils. This effect was dose-dependent: IL-5 greater than GM-CSF greater than IL-3. Light density eosinophils from most patients had a longer lifespan in culture than did normal density eosinophils, with or without the three cytokines. Eosinophil death in the absence of these cytokines occurred by apoptosis. Eosinophils from two patients did not survive when cultured with IL-5, although they survived in the presence of IL-3 or GM-CSF. IL-5, GM-CSF and IL-3 induced the expression of the activation epitope on the eosinophil ribonucleases recognized by monoclonal antibody EG2. We conclude that small amounts of IL-5, GM-CSF and IL-3 prevented programmed cell death in human blood eosinophils and induced the expression of the activation forms of eosinophil ribonucleases. We suggest that differences in the capacity of normal and light density eosinophils to survive in culture, and in the ability of eosinophils from some patients to respond to IL-5 could account for variations in the severity of disease seen in patients with persistent eosinophilia.