Smaller tuberculin test induration sizes suggest eligibility for tuberculosis chemoprophylaxis in HIV-seropositive than in HIV-seronegative persons. To determine whether human immunodeficiency virus (HIV) infection is associated with induration size among tuberculin reactors, a cross-sectional study of HIV-seropositive and -seronegative drug users was performed. Twenty-four of 160 (15%) HIV-seropositive and 68 of 284 (24%) HIV-seronegative patients had reactions to purified protein derivative (PPD) of > or = 2 mm (OR = 0.56, 95% CI 0.32 to 0.96). However, the prevalence of tuberculin reactivity was equal among nonanergic subjects with and without HIV infection. Median induration size was similar among HIV-seropositive (20.5 mm) and -seronegative (17.5 mm) reactors. Thus, although HIV-seropositive patients were less likely, due to cutaneous anergy, to be PPD reactors, induration size was not associated with HIV infection among reactors. Although using a reduced cutpoint to determine suitability of chemoprophylaxis in HIV-seropositive persons may be prudent, the logical assumption that the loss of specificity this entails is accompanied by an increase in sensitivity for detecting Mycobacterium tuberculosis infection remains to be proved.