Sixty patients considered at risk for acquired immune deficiency syndrome (AIDS) were referred for evaluation of generalized lymphadenopathy. All patients were seropositive for antibody to human T-lymphotropic virus type III (HTLV-III). Multiple lymph node biopsies from different nodal areas were performed. The results were evaluated in order to see if the diagnostic yield is increased by the performance of multiple lymph node biopsies. In no case was additional diagnostic information provided by performing multiple biopsies. In patients with diffuse lymphadenopathy who are at risk for AIDS, single node excisional biopsy is indicated to rule out opportunistic infection or/and tumor.