Primary human immunodeficiency virus (HIV) infection is a rarely diagnosed disease. The intestinal lymphocyte population represents a primary target of infection, virus replication, as well as cell infiltration and activation. The purpose of this study was to describe a patient suffering from esophageal giant ulcer as a clinical manifestation of primary HIV. In the present case of primary HIV infection a giant ulcer of the esophagus was diagnosed as the clinical manifestation. An upper endoscopy was performed and the biopsy specimens were further processed for immunohistochemical stainings characterizing the cellular infiltrate as well as cytokine production. In addition, seroconversion was documented and total viral load was determined. The esophageal ulceration presented the clinical manifestation of primary HIV infection since other causes of esophageal ulcerations could be excluded. The ulceration revealed an inflammatory infiltrate consisting of both CD4(+) and CD8(+) T cells. The vast majority of these cells expressed the activation marker CD38 and several cells showed interferon-gamma and interleukin-2 production. Furthermore, a substantial number of tissue infiltrating CD8(+) T cells expressed the cytotoxic molecule perforin. In addition, the HIV antigen p24 could be detected in the inflammatory infiltrate. Subsequent steroid treatment resulted in a relief of symptoms and healing of the ulcerations. These observations strongly suggest that infiltration of activated T cells plays a crucial role in the pathogenesis of giant ulcers during primary HIV infection.