Patients infected with the human immunodeficiency virus (HIV) are subject to infections and neoplasms, which frequently result in palpable or radiologically identified masses. Fine-needle aspiration (FNA) offers a rapid, simple, and cost effective approach for diagnosis of these masses. During a 2-yr period, 396 aspirates were performed on 362 HIV-infected patients within the LAC-USC Medical Center. Adequate material was obtained from 84% of the FNA, allowing the etiology of the mass to be determined in 90% of the cases by means of a combination of cytologic, microbiologic, and immunocytochemical procedures. Significant pathologic processes identified in these patients by means of FNA included reactive lymphoid proliferations (35%), abnormal lymphoid proliferations (12%), infections (12.5%), cystic (5.5%) and inflammatory processes (5%), nonlymphoid malignancies (4%), and salivary gland pathology (1%). We conclude that FNA is an appropriate initial diagnostic procedure in HIV positive patients presenting with mass lesions.