Background: The immune mechanism of gelatin allergy, especially the participation of T H1 and T H2 cells and their cytokine secretion, has not been investigated. Objective: We investigated the characteristics of T lymphocytes from patients allergic to gelatin-containing vaccine by secondary in vitro stimulation of circulating mononuclear cells with gelatin. Methods: We studied 8 children with a history of immediate-type reactions and 8 with nonimmediate-type reactions after inoculation of gelatin-containing vaccine. The expression of IFN-γ (T H1 ), IL-2 (T H1 ), IL-4 (T H2 ), and IL-13 (T H2 ) mRNA was examined semiquantitatively by using a reverse transcriptase PCR. IgE antibody to bovine gelatin was measured with the fluorometric ELISA system, and gelatin-specific T-cell responses were detected by an in vitro lymphocyte proliferation assay. Results: Patients with an immediate reaction all had gelatin-specific IgE antibody, whereas others did not. However, all patients exhibited positive T-lymphocyte responses specific to gelatin. Lymphocytes from subjects with nonimmediate-type reactions generally expressed very weak or sometimes no IFN-γ, IL-2, or IL-13 genes and especially no IL-4 gene. On the other hand, the lymphocytes of subjects with immediate-type reactions significantly expressed not only IL-4 and IL-13 but also IFN-γ and IL-2 mRNA. Conclusion: Our observations suggest that both gelatin-specific T H2 and T H1 responses are involved in the pathogenesis of the immediate reaction to gelatin. The gelatin-specific IL-4 and/or IL-13 responses consistently observed in patients with an immediate reaction may be associated with the production of gelatin-specific IgE antibody. (J Allergy Clin Immunol 1999;103:276-81.)