Volatile organic compounds are commonly off gassed from various building materials and can induce sick building syndrome. Volatile organic compounds such as formaldehyde, xylene and toluene are known as toxic agents in immune cells. Human leukocytes, particularly, neutrophils and eosinophils play important roles in the regulation of immune responses. In this study, we investigated the toxic effects of formaldehyde, ortho-xylene (o-xylene), para-xylene (p-xylene) and toluene on the apoptosis of neutrophils and eosinophils isolated from the blood of healthy donors. Formaldehyde increased the constitutive apoptosis of neutrophils and eosinophils. o-xylene, p-xylene and toluene increased the spontaneous apoptosis of eosinophils, but not that of neutrophils. Formaldehyde increased the protein level of IL-8 in neutrophils and eosinophils, and suppressed the MCP-1 expression in neutrophils. The release of IL-6 from neutrophils was diminished by volatile organic compounds used in this study. In conclusion, formaldehyde, xylene and toluene elevate the apoptosis of neutrophils and eosinophils, and regulate the release of cytokine and chemokine in neutrophils and eosinophils. These results indicate that formaldehyde, xylene and toluene have a cytotoxicity in human neutrophils and eosinophils and may damage the modulation of immune responses.