Immunocompromised patients demonstrate a wide variety of idiopathic cutaneous and mucosal lesions including dermatitis, gastrointestinal and genital tract ulcerations, and recurrent aphthous stomatitis. The overall objective of this research program is to evaluate the pathogenesis of mucosal inflammation associated with immune dysregulation in HIV-infected patients with aphthous lesions. A randomized, controlled clinical trial was initiated which serves as a vehicle for several lines of inquiry directed towards investigating the pathogenesis of oral aphthous ulcers, which are spontaneous, recurrent mucosal ulcerations of unknown etiology, and which are persistent and debilitating in persons with HIV/AIDS. The objectives are to: 1) assess clinical outcomes in a pharmacologic evaluation of a novel topical thalidomide preparation, 2) evaluate the contribution of the local inflammatory process to the pathogenesis of aphthous ulcers in HIV-infected patients by examining the cellular and molecular effects of thalidomide on inflammatory cells and lesion progression and healing, 3) examine the effect of the chronic inflammation (aphthous lesions) and its treatment with thalidomide on HIV load systemically and in the oral cavity, and 4) evaluate presence of pathogens, including HIV, as potential causative agents for the observed mucosal immune response.