Studies conducted before the introduction of highly active antiretroviral therapy (HAART) suggested that the risk of Hodgkin lymphoma in persons with human immunodeficiency virus (HIV) infection was increased. However, little is known about the features of this malignancy in patients receiving HAART. From January 1996 through December 2001, 23 cases of Hodgkin lymphoma were diagnosed among 3,945 HIV infected patients attending the Harris County Hospital District in Houston, Texas. Twenty (87%) of the HIV-infected patients diagnosed with Hodgkin lymphoma were receiving HAART and 3 (13%) were naive to antiretroviral therapy. The incidence per 1,000 patients of Hodgkin lymphoma in patients receiving HAART was 6.5. The median duration of HAART before the diagnosis of Hodgkin lymphoma was 16 months (range, 7-22 mo). The median CD4 cell count was 235 cells/mm(3) (range, 189-325 cells/mm(3)) for the 20 HIV-infected patients receiving HAART at the time of diagnosis of Hodgkin lymphoma and 90 cells/mm (range, 72-120 cells/mm(3)) for the 3 patients naive for antiretroviral therapy. Among patients with Hodgkin lymphoma receiving HAART, 50% (10/20) had an HIV-RNA viral load in plasma below the level of detection <400 copies/mL). Chemotherapy was administered to all patients, but a complete response was achieved in 30% (6/20) of the patients receiving HAART and 0% (0/3) of the patients naive to antiretroviral therapy. These results suggest that Hodgkin lymphoma has a low incidence in HIV-infected patients receiving HAART, but the malignancy is an aggressive disease with unfavorable clinical outcome in these patients.