We prospectively studied the utility of fine needle aspiration (FNA) to diagnose non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) in patients with human immunodeficiency virus (HIV) infection and lymphadenopathy. Twenty-one patients with a clinical evidence of lymphoma underwent 24 FNA and site-specific tissue biopsies. Twenty-two of the 24 biopsy results were consistent with a malignant lymphoproliferative neoplasm: NHL (19 cases), HD (two cases), and T-cell lymphoma (one case). Two biopsies showed reactive lymphoid hyperplasia consistent with a clinical diagnosis of persistent generalized lymphadenopathy. There was an 87% correlation (21 of 24) between FNA and biopsy diagnoses. Eighteen of the 19 biopsy-confirmed NHL cases were diagnosed with FNA. Both cases of HD and the one T-cell lymphoma were also diagnosed with aspirate material. In conclusion, the FNA in HIV-infected individuals with suspected malignant lymphadenopathy is highly sensitive (95%). The FNA, when used in conjunction with the clinical appearance, is a useful tool in the management of HIV infection and lymphadenopathy.