Background: There is evidence that IL-16, a cytokine that induces chemotactic responses in CD4+ T cells, eosinophils, and dendritic cells, plays an important role during different types of cutaneous inflammatory responses, including allergic contact dermatitis (ACD) and atopic dermatitis (AD). Objectives: We sought to test for association between a promoter polymorphism in the IL16 gene (T to C transition at position -295) and ACD and AD, respectively. Methods: IL16 -295 genotypes were determined in samples from 2 separate case-control studies with white individuals. The first study included healthy individuals (n = 310) and patients with ACD (n = 86). These patients were polysensitized as defined by a contact sensitization to para-substituted aryl compounds and at least one other structurally unrelated allergen. The second study comprised healthy subjects (n = 214) and patients with AD (n = 94). Results: IL16 -295 genotypes were differently distributed among polysensitized and healthy control subjects (P = .0021). In particular, the IL16 -295*C/C genotype was overrepresented among polysensitized individuals (7.0% vs 1.0% in the control group; odds ratio, 7.68; 95% CI, 1.59-48.12). In contrast, there was no evidence for an association between the IL16 -295 polymorphism and AD. Conclusion: The IL16 -295 promoter polymorphism might influence susceptibility to contact allergy.