Kaposi's sarcoma-associated herpesvirus, the viral agent of Kaposi's sarcoma, is associated with two lymphoproliferative disorders: primary effusion lymphoma and multicentric Castleman's disease. To identify other lymphoproliferative conditions linked with Kaposi's sarcoma-associated herpesvirus, we studied non-Hodgkin's lymphomas arising in individuals with AIDS-associated Kaposi's sarcoma. Formalin-fixed tissues from 24 such lymphomas were examined. As expected, two primary effusion lymphomas were Kaposi's sarcoma-associated herpesvirus-positive, with immunohistochemistry demonstrating the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen in the nuclei of all neoplastic cells. Additionally, three of seven evaluable cases of the immunoblastic variant of diffuse large B-cell lymphoma (immunoblastic lymphoma) showed similar latency-associated nuclear antigen staining. These Kaposi's sarcoma-associated herpesvirus-positive immunoblastic lymphomas resembled primary effusion lymphoma histologically but were not known to involve body cavities (sites included lymph nodes, soft tissues of the neck, and spleen). Notably, 5-20% of the neoplastic cells in the Kaposi's sarcoma-associated herpesvirus-positive immunoblastic lymphomas also showed cytoplasmic staining for viral interleukin-6, a biologically active cytokine homologue found in primary effusion lymphoma. We conclude that Kaposi's sarcoma-associated herpesvirus is present in some immunoblastic lymphomas in persons with AIDS-associated Kaposi's sarcoma.