We compared the clinical features of disease due to tuberculosis and to Mycobacterium avium complex (MAC) in 94 patients with human immunodeficiency virus infection. Tuberculosis preceded the diagnosis of acquired immunodeficiency syndrome in 26 (67%) of 39 cases, compared with none of 55 with MAC infection. Chest roentgenographic findings suggested mycobacterial infection in 24 (83%) of 29 patients with pulmonary tuberculosis, compared with 7 (25%) of 28 with MAC infection. Sputum smears revealed acid-fast bacilli in 19 (83%) of 23 patients with pulmonary tuberculosis, but only 4 (16%) of 25 cases of pulmonary MAC infection. In 39 patients with tuberculosis, lymphadenitis and pleuritis were present in 13 (33%) and 8 (20%), respectively, but occurrence was rare in patients with MAC infection. In contrast, mycobacteremia was more frequent in MAC infection, occurring in 47 (85%) of 55 cases. In 5 patients, tuberculosis was unsuspected and probably contributed to death. These findings suggest that clinical features often distinguish tuberculosis from MAC infection in patients with human immunodeficiency virus infection. In addition, more intensive diagnostic use of sputum acid-fast smears may improve the outcome in patients with tuberculosis.