Extracts of purified human eosinophils had a mean concentration of 72 fmol of immunoreactive vasoactive intestinal peptide and 21 fmol of substance P per 10(7) eosinophils, that were significantly higher than the content of immunoreactivity of the same neuropeptides in neutrophils, mononuclear leukocytes, and platelets. In contrast, the lower concentrations of calcitonin gene-related peptide and somatostatin were similar in extracts of all leukocytes. Chromatography of the peptides from eosinophils confirmed their identity with vasoactive intestinal peptide and substance P from neuroendocrine sources. Stores of some neuropeptides may endow eosinophils with unique roles in host defense and hypersensitivity reactions.