Many studies have documented that, in cutaneous hypersensitivity (CHS), 0.5% - 3% oxazolone (OXA) induces keratinocyte hyperplasia, cell infiltration into the dermis, Th1/Th2 cytokines and lymph node cell proliferation. To evaluate these parameters in a chronic, low dose exposure paradigm, B6,129 mice were sensitized and challenged with 0.5%, 0.1 % or 0.05% OXA (week 1), and challenged 3 consecutive days each week for 5 weeks. Ear thickness increased significantly with application of 0.5% OXA only and declined toward baseline by week 6. Histological analysis of challenged ears revealed dose-dependent keratinocyte hyperplasia and inflammatory cell infiltration that peaked in weeks 2 and 3 and decreased in magnitude by week 5. An in situ apoptosis assay revealed significant increase in apoptotic cells in the dermis in week 3, compared to week 1. We measured dose-dependent increases in IL-1y, IFN-y and IL-4, however IFN-y levels declined significantly in week 3, whereas IL-1-B and IL-4 remained elevated. 0.5% OXA, but not 0.1 % or 0.05%, increased TNF-a significantly. OXA did not induce in vitro lymph node cell proliferation for any concentration of chemical after a single challenge dose (week 1) and no cell proliferation for 0.05% OXA at any time point. 0.5% OXA induced 4.8 and 10.5 fold increases in cell proliferation at weeks 2 and 3, but not at week 6. 0.1 % OXA induced a 3 fold increase in proliferation at week 3. These data demonstrate that 0.5% and 0.1 % OXA stimulate CHS for 2 to 4 weeks but that the cutaneous immune response to OXA becomes insensitive to OXA stimulation after 5 to 6 weeks of chronic, low dose chemical exposure.