Non-Hodgkin-lymphoma (NHL)-most frequently high grade B-cell lymphoma-occurs in 5-10% of individuals with HIV-infection. The gastrointestinal tract (GIT) is the most frequent extranodal site of the disease. The optimal therapy for HIV-related lymphoma remains a matter of controversy. In a retrospective analysis we found gastrointestinal lymphoma in ten of 306 HIV-infected patients (3.3%) with a median CD4-count of 92/microliter at time of diagnosis. Median survival for the chemotherapy treatment group was 15 months. The high incidence of gastrointestinal NHL prompted us to commence a prospective survey on diagnostic procedures, therapy and outcome of patients with HIV-infection and gastrointestinal symptoms. 93 of 341 HIV-infected patients with gastrointestinal symptoms were examined by endoscopy. In selected patients we used in addition endoscopic ultrasound (EUS) for visualization and staging before and after chemotherapy. NHL of the GIT was detected in seven of 93 endoscopically examined patients (7.5%). All patients were treated with CHOP initially. Mean survival time was ten months, mean CD4-count at diagnosis 193/microliter (range 0-417). Our results indicate that the diagnosis of gastrointestinal lymphoma should be considered in any HIV-infected patient presenting with unexplained gastrointestinal symptoms. In this group of patients NHL was detected in 7.5% of cases. The use of EUS improves the staging procedure before therapy. Treatment with CHOP resulted in relatively high remission rates and was associated with a low rate of treatment-induced myelosuppression.