Excess hydrocortisone (HC) evokes neutrophilia and eosinopenia in man. In addition, the hormone enhances human granulopoiesis in vitro at physiological as well as pharmacological concentrations. This study addressed the prospect that HC exerts opposite effects on the precursors of neutrophils and eosinophils, stimulating the former and inhibiting the latter. Experiments conducted on unseparated bone marrow (BM) cells demonstrated an increase in eosinophil clonogenesis in vitro with the addition of HC to the culture system. Secondary cultures, established from such primary harvests, revealed that HC had a direct impact on the clonogenic cells. Furthermore, administration of HC to normal subjects, at a dose which resulted in consistent eosinopenia, prompted an increase in the generation of eosinophil clones from peripheral blood cells ex vivo. Thus the hormone stimulates production of both neutrophils and eosinophils. Previous reports of opposite effects appear to have resulted from deficiencies of growth factors in the cell cultures. The contrasting effects of HC on neutrophil and eosinophil concentrations in the peripheral blood are more likely due to opposite effects on the distribution of these terminally differentiated cells in the circulation and extravascular tissues.