To determine the factors associated with the duration of wheals in urticaria, we carried out a quantitative study of mast cells and eosinophils in both peripheral bloods and skin lesions. The percentage of cytoplasmic vacuolation, indicating a result of eosinophil degranulation of all types of specific granules of circulating eosinophils was significantly increased in the long-duration group compared with the short-duration group. Many extracellular free eosinophil granules were observed in the vicinity of disrupted eosinophils in the long-duration wheals. On the other hand, the short-duration wheals had few free eosinophil granules. The number of free eosinophil granules and the percentage of free eosinophil granules to eosinophils were significantly different between the long- and the short-duration wheals, whereas there was no significant difference between the early stage and the late stage of the long-duration wheals. The numbers of all inflammatory cells, eosinophils, and activated mast cells were increased in the late stage of the long-duration wheals. These findings suggest that free eosinophil granules liberated from infiltrating eosinophils by some stimulus may provoke the persistent activation of mast cells, and the mast-cell-derived mediators may induce the persistent state of inflammation in the long-duration wheals.