Our recent studies showed that exposure to mixed indoor air pollutants in a newly decorated residential apartment induced expanded simple tandem repeats (ESTR) mutations in mice, and the mutations were mainly inherited from the paternal germ line. Formaldehyde (FA) is a type of major volatile organic chemical (VOC) present in indoor air, and a constituent known to be associated with sick building syndrome. In the present study, mice were exposed to different concentrations of FA (0, 2, 20, or 200 mg/m(3)). The germline mutations were detected in their offspring using three ESTR probes, Ms6-hm, Hm-2, and MMS10. Data indicated that mice exposed to 200 mg/m(3) FA demonstrated a significant elevation in ESTR mutations, which is due primarily to an increase in mutations inherited through the paternal germ line. These results suggest that FA induced ESTR mutations in mice. It is postulated that single FA exposure might be a useful model to identify indoor air mixture exposure-induced heritable DNA damage.