Background: Specific T-cell responses to food antigens have been described in children with atopic dermatitis (AD). However, a subgroup of adolescent and adult patients still experiences food-responsive AD. Objective: This study was designed to evaluate lymphocyte responses to bovine casein in adult patients with AD. Methods: The stimulatory capacity of lipopolysaccharide-depleted bovine casein was tested in proliferation assays and in limiting dilution assays. Casein-specific T-cell clones (TCCs) were generated and characterized. Results: Higher proliferative responses to casein and modulation of cytokine receptors were observed in patients with milk-responsive AD compared with individuals without clinical reactions on milk ingestion. The results did not correlate with the amount of casein-specific IgE in the serum. The frequencies of T cells that grew in the presence of casein or house dust mite antigens were similar. Only 27% of CD4⁺ casein-specific TCCs from these patients, but the majority of house dust mite–specific TCCs, produced IL-4 on mitogen stimulation. Interferon-γ, on the other hand, was produced by the majority of TCCs with both specificities. Conclusion: A specific T-cell–mediated immune response to casein can be found in the blood of adolescent and adult patients with milk-related exacerbation of AD. In contrast to house dust mite–specific T cells, casein-specific T cells of adult patients who respond to cow's milk with worsening of AD produce little or no IL-4. (J Allergy Clin Immunol 1997;99:124-33.)