It has been demonstrated previously that a selective pattern of mitogen-inducible interleukin-4 (IL-4) production becomes apparent in mice after temporal evolution of the immune response to different classes of chemical allergen. Mitogen-stimulated draining lymph node cells (LNC) isolated after primary exposure to both the respiratory allergen trimellitic anhydride (TMA) and oxazolone, a contact allergen, secreted similar amounts of IL-4. Following secondary exposure, however, TMA, but not oxazolone, caused a marked increase in IL-4 production, consistent with the stimulation by TMA of a T-helper type-2 (Th2)-type response. In the present study, cytokine production characteristic of Th1 (interferon-gamma; IFN-gamma) and Th2 (IL-4 and IL-10) cell activation was examined following chronic exposure of mice to allergen over a 13-day period. In accord with previous studies, chronic exposure to TMA, but not to oxazolone, resulted in a substantial potentiation of mitogen-inducible IL-4 secretion. In addition, spontaneous IL-10 production by TMA-activated LNC was significantly higher than by cells prepared from oxazolone-exposed animals. The lower levels of Il-4 and IL-10 elaborated by oxazolone-activated LNC were not attributable to a reduced potential to secrete cytokine per se, as significantly more IFN-gamma was produced compared with TMA-activated LNC. It is proposed that these divergent cytokine production patterns reflect the selective stimulation of Th1- and Th2-type responses by contact and respiratory chemical allergens.