Although Glutaraldehyde (Glut) has been demonstrated to be a moderate contact sensitizer, numerous cases of occupational asthma related to Glut exposure have been reported. The purpose of these studies was to examine the dose-response relationship between Glut exposure and the development of T cell-mediated vs. IgE- mediated responses. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.75% to 2.5%. A concentration-dependent increase in lymphocyte proliferation was observed with EC3 values of 0.072% and 0.089% in CBA and BALB/c mice, respectively. The mouse ear swelling test (MEST) was used to evaluate the potential for Glut to elicit IgE (1/2 h post challenge) and contact hypersensitivity (24 and 48 h post challenge) responses. An immediate response was observed in animals induced and challenged with 2.5% Glut, whereas animals induced with 0.1% or 0.75% and challenged with 2.5% exhibited a delayed response 48 h post challenge. IgE-inducing potential was evaluated by phenotypic analysis of draining lymph node cells and measurement of total serum IgE levels. Only the 2.5% exposed group demonstrated a significant increase (P < 0.01) in the percentage of IgE(+)B220(+) cells and serum IgE. Following 3 days of dermal exposure, a significant increase in IL-4 mRNA in the draining lymph nodes was observed only in the 2.5% exposed group. These results indicate that the development of an immediate vs. a delayed hypersensitivity response following dermal exposure to Glut is at least in part mediated by the exposure concentration.