We review the clinical features and histopathologic changes observed in 69 cases of lymphadenopathy in homosexual men. The most common pattern seen was that of florid reactive follicular hyperplasia (43 cases). A peculiar and distinctive lysis of the germinal centers, a phenomenon we have termed "follicle lysis," was noted in 25 cases. Eighteen of these lymph nodes also contained sinusal collections of "monocytoid" cells and neutrophils and six showed focal dermatopathic changes. Seven cases were characterized by a lymphocyte-depleted pattern with only occasional regressively transformed germinal centers. Nine patients were found to have involvement of their lymph nodes by Kaposi's sarcoma; malignant lymphomas were encountered in 10 patients (eight with Hodgkin's disease and two with non-Hodgkin's lymphomas). Polykaryocytes (multinucleated giant cells) were observed in germinal centers or interfollicular areas within the lymph nodes of four patients. Limited clinical follow-up was available but the lymphocyte-depleted group appeared to have a more aggressive clinical course (three patients in this group developed pneumocystis pneumonia, two had mycobacterial infections and one cutaneous Kaposi's sarcoma). The diverse nature of these findings and the potential for treatment of certain patients (i.e., those with malignant lymphomas and mycobacterial infections) underlines the importance of lymph node biopsy in all cases of unexplained lymphadenopathy in homosexuals and other individuals susceptible to the acquired immunodeficiency syndrome (AIDS). The histopathologic findings may also serve to identify a subgroup of these patients at increased risk to develop more severe AIDS-related complications.