To examine the relationship between latent Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV) disease progression, two studies were done among a cohort of HIV-infected injecting drug users. First, the decline in CD4 cell count after baseline tuberculin skin testing was prospectively compared for 37 tuberculin-positive (induration > or = 5 mm) and 284 tuberculin-negative (induration < or = 2 mm) persons. After adjustment for baseline immune function, the mean 6-month CD4 cell decline was not significantly different (34.5 vs. 45.6 cells, respectively, P = .14). Second, the plasma HIV burden at baseline skin testing was compared for 33 tuberculin-positive cases and 33 matched tuberculin-negative controls. HIV RNA was detected in 8 cases and 10 controls (odds ratio = 0.67, 95% confidence interval = 0.19-2.36). Among the 14 pairs with HIV detected in > or = 1 member, the HIV concentration was higher for the case in 4 and for the control in 10 (P = .18). These findings suggest that unlike active tuberculosis, latent M. tuberculosis infection does not hasten HIV progression.