Background: A new antibacterial quinolone, sparfloxacin (SPFX), frequently causes photosensitive dermatitis and sometimes induces a treatment-resistant lichenoid tissue reaction (LTR). Objective: We attempted to determine the factors that induce LTR in SPFX-induced photodermatitis. Methods: Thirteen patients with SPFX photosensitive dermatitis were studied clinically and histopathologically. Results: Six of the 13 patients had acute dermatitis with epidermal spongiosis and focal epidermal HLA-DR and intercellular adhesion molecule–1 (ICAM-1) expression with CD4⁺ cell infiltration. The other seven displayed LTR with basal cell liquefaction degeneration and diffuse epidermal HLA-DR and ICAM-1 expression associated with CD8⁺ cells. The seven patients with LTR were exposed to UV and SPFX for more than 2 weeks after the appearance of their initial eruption, whereas the six patients with acute dermatitis were treated within 2 weeks. The acute dermatitis lesions cleared significantly within 2 weeks, but the LTR lesions persisted for more than 6 weeks. Conclusion: Patients with quinolone-induced photosensitivity should be treated within 2 weeks of onset to prevent LTR. (J Am Acad Dermatol 1998;38:945-9.)