We investigated the ultrastructural characteristics and the granule major basic protein (MBP) content of hypodense eosinophils from patients with the hypereosinophilic syndrome who had at least 90% hypodense eosinophils in their peripheral blood and compared these cells to normodense eosinophils from normal persons. The hypodense cells (density less than 1.082) contained significantly less MBP than normodense (density greater than 1.082) eosinophils (P less than .001) as measured by radioimmunoassay (RIA). Electron microscopic examination demonstrated a mean of 25.0 +/- 4.4 (X +/- 1 SD) granules per hypodense cell, compared to 30.6 +/- 8.4 granules per cell in the normodense group (P less than .1). The most striking difference between the hypodense and normodense eosinophils was the small individual granule size (X = .14 +/- .05 v .26 +/- .05 micron 2, respectively, P less than .001), and the smaller total granule area (3.2 +/- 1.8 vs 7.7 +/- 3.1 micron 2, respectively, P less than .001). Because the cytoplasmic areas were similar in the two groups, the mean percent area of cytoplasm occupied by granules was significantly lower in the hypodense group (P less than .001). The finding of consistently smaller granules in the presence of equal or fewer granules per cell in the hypodense eosinophils may explain the lower MBP content and thus provide a morphologic basis for the low density of eosinophils in patients with the hypereosinophilic syndrome.