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To evaluate the relationship between the clinical presentation of tuberculosis and the CD4 cell count in patients with human immunodeficiency virus (HIV) infection, we evaluated clinical and laboratory features of 97 HIV-infected patients with tuberculosis in whom CD4 cell counts were available. Extrapulmonary tuberculosis was found in 30 (70%) of 43 patients with ≤ 100 CD4 cells/μL, 10 (50%) of 20 patients with 101 to 200 CD4 cells/μL, seven (44%) of 16 patients with 201 to 300 CD4 cells/μL, and five (28%) of 18 patients with > 300 CD4 cells/μL (p = 0.02). Mycobacteremia was found in 18 (49%) of 37 patients with ≤ 100 CD4 cells/ μL, three (20%) of 15 patients with 101 to 200 CD4 cells/μL, one (7%) of 15 patients with 201 to 300 CD4 cells/μL, and none of eight patients with > 300 CD4 cells/μL (p = 0.002). Acid-fast smears were more often positive in patients with low CD4 cell counts. Positive tuberculin skin tests were more common in patients with high CD4 counts. On chest roentgenograms, mediastinal adenopathy was noted in 20 (34%) of 58 patients with ≤ 200 CD4 cells/μL and four (14%) of 29 patients with > 200 CD4 cells/μL (p = 0.04). Pleural effusions were noted in six (10%) of 58 patients with ≤ 200 CD4 cells/μL and eight (28%) of 29 patients with > 200 CD4 cells/μL (p = 0.04). The CD8 cell counts did not correlate with the manifestations of tuberculosis. We conclude that, in HIV-infected patients, markers of severe tuberculosis, such as mycobacteremia and positive acid-fast smears, are more common in those with low CD4 cell counts. Features dependent on delayed-type hypersensitivity responses, such as positive tuberculin skin tests and tuberculous pleuritis, are more common in patients with higher CD4 cell counts. These findings suggest that CD4 cells play a central role in limiting the severity of tuberculosis.