Abstract Cutaneous immune reactions to soluble antigens, such as drugs, are common, but their precise pathomechanism remains unclarified. To this end, we newly developed a murine model for skin eruptions against soluble antigens using ovalbumin (OVA)-specific TCR transgenic line, OT1. OT1 T cells were adoptively transferred to naïve mice and were immunized with OVA/CFA. Five days later, a skin inflammation was induced to the right ear with topical PMA treatment, which induced skin-resident memory T cells (TRM). Two weeks after PMA-painting, a large number of CD103+CD69+ OT1-TRM were found in the epidermis of PMA-painted site, whereas only a marginal number of OT1 T cells were detected in the untreated left ear. Then, OVA peptide was injected intravenously, which exhibited immediate ear swelling response only in the right ear where OT1-TRM exist in the epidermis. Five days after the systemic administration of OVA peptide, CD44+CD62L- effector memory OT1 T cells (TEM) were significantly increased in the blood and, intriguingly, were detected in the dermis of the untreated left ear. In addition, a repeated intravenous administration of OVA peptide developed chronic necrotic skin lesion even without extrinsic stimuli. These observations implicate respective roles of TRM and TEM in cutaneous immune responses: antigen-specific TRM in the epidermis cause immediate and localized skin eruptions, whereas TEM infiltrate from the blood into the dermis and induce chronic disseminated dermatoses.