To evaluate the etiology and differential features of intrathoracic lymphadenopathy (LAD) in HIV patients, chest computed tomography (CT) records from an 18-month period were reviewed to identify all HIV-positive patients with intrathoracic LAD (nodal size > or = 1 cm). Medical records were reviewed for the documentation of specific diseases causing LAD and the CD4 count at the time of imaging. Of 45 HIV-positive patients with LAD, 40 had specific diagnoses including 22 (55%) infections and 17 (43%) tumors; one patient had both (3%). Mycobacterial disease accounted for 78% of infections; five cases were secondary to bacterial pneumonia and sepsis. Of tumors, lymphoma (7 cases, 39%) was most common, followed by lung cancer, germ cell tumors, and Kaposi's sarcoma. Mean CD4 cell count in patients with tumors was much higher than in patients with infections (314 vs. 62, p < .01). Patients with tumors were somewhat more likely than patients with infections to demonstrate axillary adenopathy (29 vs. 5%, p = .068). Cavitary disease was only observed in patients with infections (27%, p < .03). CT and clinical findings may help direct the differential diagnosis of LAD in AIDS, and promote expedient definitive diagnosis and therapy.