We examined the effect of diesel exhaust particle (DEP) extracts on oral tolerance in mice. For this examination, a single DEP sample was consecutively extracted with hexane (HEX-DEP), benzene (BEN-DEP), dichloromethane (DIC-DEP), methanol (MET-DEP), and 1 M ammonia (AMM-DEP). Residues unextracted (UNE-DEP) with the last extraction solvent 1 M ammonia were also used to test their ability to induce oral tolerance. To immunize mice, hen egg lysozyme (HEL) emulsified with an equal volume of CFA was injected sc (day 0). Oral tolerance was induced by feeding 10 mg HEL on days -5, -4, -3, -2, and -1. DEP, each DEP extract, and UNE-DEP were intranasally administered immediately after each feeding of HEL. The results showed that oral administration of HEL markedly suppressed production of anti-HEL IgG antibodies as well as proliferative responses of spleen cells to HEL. The suppression of anti-HEL IgG antibody production and the cell proliferation by the oral antigen was significantly blocked by DEP, DIC-, AMM-, and UNE-DEP. Neither HEX-, BEN-, nor MET-DEP modulated the orally induced suppression of these immune responses. When the levels of anti-HEL IgG2a antibodies and IFN-gamma (Th1 responses) and anti-HEL IgG1 antibodies and IL-4 (Th2 responses) were determined, DEP and DIC-DEP diminished the suppression of both Th1 and Th2 responses observed following oral administration of HEL. In contrast, UNE- and AMM-DEP prevented the reduction of Th1 but not Th2, and Th2 but not Th1 oral tolerance, respectively. Thus, UNE-DEP appears to contain compounds that block induction of Th1 but not Th2 oral tolerance, whereas AMM-DEP have compounds that abrogate induction of Th2 but not Th1 oral tolerance. DIC-DEP, as well as DEP, appear to contain components that block induction of both Th1 and Th2 oral tolerance. As oral tolerance is thought to play a critical role in preventing Th1 as well as Th2 food allergy, the blockade of oral tolerance by these DEP extracts suggests that DEP may contain compounds different in hydrophobicity associated with the cause of such adverse immunologic responses to food proteins.