Histoplasma capsulatum (HC) is a thermally dimorphic ascomycete that is a significant cause of respiratory infections (> 80%) in endemic areas (Midwest and southeast USA), but infections are rare in non-endemic areas. Most primary HC infections are subclinical or self-limited. While reactivation Histoptasmosis has been reported in the setting of immunosuppression, it remains unclear whether remote primary latent infection represents risk of endogenous reactivation after anti-tumor necrosis factor (TNF)-alpha therapy [Yusuf H, Craig GT, Allan D. Disseminated histoplasmosis presenting with oral lesions-report of a case. Br J Oral Surg 1979;16(3):234-40; Catanzaro A, Spitler LE, Campbell GD, Moser KM. Transfer factor therapy for histoplasmosis in a patient with Hodgkin's disease. Arch Intern Med 1981;141(4):533-7; Fredricks DN, Rojanasthien N, Jacobson MA. AIDS-related disseminated histoplasmosis in San Francisco, California. West J Med 1997;167(5):315-21]. We report a case of a patient who developed reactivation Histoplasmosis after receiving anti-TNF-alpha. To our knowledge, this is the first clear report of reactivation of "latent" Histoplasmosis after anti-TNF-alpha therapy. (c) 2005 Elsevier Ltd. All rights reserved.