We previously showed the median duration of positive patch test reactions to nickel sulfate(5% pet) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 Days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal down regulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n= 8) and normally resolving allergic patch lest reactions (NRAPTR) (n= 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.8μg/g, μg/g, range 0.25–3.87 μg/g, mean 0.83μg/g, 95% CI 0 35–1.31) and NRAPTR (median 0.58 μg/g, range 0.2 1.85 μg/g, mean 0.88 μg/g, 95% CI 0.02 1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2>CD8>CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CDI and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immuno-cytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.