In general, contact sensitizers have been shown to selectively induce Th1 immune responses, such as interferon-gamma (IFN-gamma) production, whereas Th2 responses, such as interleukin (IL)-4 production, were seen after exposure to respiratory allergens. However, these features may be dependent on the dose of the particular allergen. Therefore, the aim of the present study was to investigate the distinction between contact sensitizers and respiratory allergens, by establishing dose-dependent cytokine profiles. The contact allergens 2,4- dinitrochlorobenzene (DNCB), hexyl cinnamic aldehyde (HCA), and oxazolone (OXA, 4-ethoxymethylene 2-phenyloxazol-5-one) as well as the respiratory allergens fluorescein 5-isothiocyanate, phthalic anhydride, toluene diisocyanate, and trimellitic anhydride were tested. For a range of concentrations, both proliferative responses and cytokine production were established. Estimated concentrations were derived at several stimulation indices (SIs). From the estimated concentrations, IFN-gamma, IL-4, and IL-10 production as a function of stimulation indices were plotted. All four respiratory allergens showed significantly higher IL-4 and IL-10 production patterns compared to the contact allergens. Positive identification of DNCB, HCA, and OXA as contact allergens on the basis of IFN-gamma production was observed only at very high stimulation indices (SI >or= 35) for DNCB and OXA and at low SIs (SI <or= 7) for HCA. We propose that, by direct linkage of proliferation and cytokine production in a dose-response manner, distinguishing contact allergens from respiratory allergens may be improved compared to present approaches.