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In HIV-infected patients with intrathoracic lymphadenopathy, it is not known whether clinical and radiographic findings are useful in predicting a specific diagnosis. We determined the etiology and predictors of the etiology of computed tomography (CT)-diagnosed intrathoracic lymphadenopathy in HIV-infected patients evaluated from June 1993 through April 1999. Multivariate analyses were performed to determine clinical and radiographic predictors of the three most common diagnoses. Of 318 patients, 110 (35%) had lymphadenopathy on chest CT. Among these 110 patients, tuberculosis/nontuberculous mycobacterial disease (n = 31), bacterial pneumonia (n = 26), and lymphoma (n = 21) were the most common diagnoses. Multivariate analysis identified cough and necrosis of lymph nodes on chest CT as independent predictors of tuberculosis/nontuberculous mycobacterial disease. African-American race, symptoms for 1 to 7 days, dyspnea, and presence of airways disease on chest CT were independent predictors of bacterial pneumonia; symptoms for >7 days, absence of cough, and absence of pulmonary nodules on CT independently predicted lymphoma. Intrathoracic lymphadenopathy is a frequent chest CT finding in HIV-infected patients. Opportunistic infections and lymphoma are the most common causes, and specific clinical and radiographic features can suggest these particular diagnoses.