An HIV-1 seronegative man presented with odynophagia, dysphagia, diarrhea, tenesmus and a 50-lb weight loss. A large esophageal ulcer and a rectal fissure were identified endoscopically. Stool samples and biopsy specimens from the esophageal ulcer, duodenum, colon and rectum were negative for pathogens. Seronegative AIDS was suspected, and high levels of HIV-1 mRNA (> 242000 copies/mL) were detected. The esophageal ulcer responded to oral steroids and the HIV-1 infection to highly active anti-retroviral therapy (HAART). The virus isolated from the patient and an HIV-1 seropositive, asymptomatic, female sex worker with whom he had recently terminated a one-year heterosexual relationship showed sequence homology, indicating her as the source of his virus. The unusual presentation of severe gastrointestinal disease in an HIV-1 seronegative man with HIV-1 virema underscores the importance of including AIDS in the differential diagnosis of wasting syndrome (i.e., B-type symptoms such as fever, night sweats, weight loss) in patients who are HIV-1 seronegative but at risk for AIDS. © Karl Demeter Verlag im Georg Thieme Verlag KG Stuttgart.