Naive and activated T cells are known to express different adhesion molecules and are thought to exhibit different migratory patterns that result from their expression of discrete adhesion molecules. Two adhesion molecules that have been associated with differentiating naive and activated/memory T cells are CD62L (l-selectin) and CD44 (H-CAM). It has been demonstrated previously that naive T cells express a CD62L^hiCD44^lophenotype, whereas memory T cells exhibit a CD62L^loCD44^hiphenotype. The purpose of the present investigation was to determine whether chemical allergens, in contrast to irritants, would induce a CD62L^loCD44^hiphenotype on CD4 and/or CD8 T cells isolated from draining lymph nodes (DLN) of treated mice. Mice were treated on the ears for 3 consecutive days with concentrations of allergens or irritants which caused an increase in the number of DLN cells. The DLN were excised 72 hr following the final chemical treatment and cells prepared for analysis by flow cytometry. In mice treated with the allergen trinitrochlorobenzene an increase in the percentage of CD4⁺cells expressing CD62L^loCD44^hiwas observed compared to cells isolated from mice treated with the irritant benzalkonium chloride or vehicle treated mice. Mice treated with dintrochlorobenzene had an increase in the percentage of CD4⁺cells expressing CD62L^loCD44^hithat was dose dependent and peaked at 72 hr following the final allergen treatment. Concomitant with changes on CD4⁺cells, increases in the percentage of CD8⁺cells expressing CD62L^loCD44^hiwere observed with allergens, but not with irritants. Increases in the percentage of CD4⁺and CD8⁺cells expressing CD62L^loCD44^hiwere observed with other allergens including oxazolone and α-hexylcinnamaldehyde, but not the irritant sodium lauryl sulfate. These data demonstrate that allergens, but not irritants, cause a selective and reproducible increase in the percentage of CD4⁺and CD8⁺cells expressing the T cell activation/memory phenotype CD62L^loCD44^hi. Analysis of T cell activation/memory markers may be useful in differentiating allergen and irritant responses in the draining lymph nodes of chemically treated mice.