This study is a phase I, single-center, open label, randomized controlled clinical trial assessing the effect of pre-clearance of latent Mycobacterium tuberculosis (MTB) by Isoniazid, isonicotinic acid hydrazine (INH) treatment before Bacillus Calmette-Guérin (BCG) revaccination versus BCG revaccination alone on mycobacterial-specific immune responses in tuberculin skin test (TST) positive adults. Subjects initially assigned to observation prior to BCG revaccination will receive INH treatment of latent tuberculosis infection (LTBI) beginning six months after revaccination. Volunteers will include 82 healthy, TST positive human immunodeficiency virus (HIV)-uninfected, male and female persons aged 18-40 years. The primary objectives of the study are to: determine the effect of INH preclearance on the kinetics and characteristics of the specific immune response following BCG revaccination in adults with latent MTB infection (TST positive); and determine the safety and reactogenicity of BCG revaccination in TST positive adults. The secondary objectives of the study are to: determine the effect of INH preclearance and BCG revaccination on MTB-specific Th1 effector and central memory cell function; determine the effect of INH preclearance and BCG revaccination on MTB-specific Treg cell function; and determine the effect of INH preclearance and BCG revaccination on innate immune responses as measured by T cell mediated inhibition of intracellular mycobacterial growth and inflammatory cytokine production. All subjects are expected to be enrolled over 12 months. The duration of screening, enrollment, and follow-up for subjects is up to 22 months. Subjects will be randomly assigned to receive either: 6 months of INH treatment for LTBI (completed within no more than 7 months) followed by intradermal BCG revaccination or 7 months of observation (run in period) followed by intradermal BCG revaccination followed after 6 months of observation by 6 months of INH treatment for LTBI. Both groups will receive their BCG vaccinations during the same time period. Volunteers will be evaluated at 7 and 14 days and 1, 3, 6 and/or 12 months after BCG revaccination and each month of INH therapy and the end of study for safety, reactogenicity and immunogenicity. Blood for immunologic studies will be drawn at study enrollment for subjects, just prior to BCG revaccination, and 1, 2 weeks and 1, 3 and either 6 or 12 months (depending on which study arm) after BCG vaccination, and months 1, 3, 6 of INH therapy and the end of study for measurement of MTB specific T cell responses. Both treatment arms will be followed for safety and immunogenicity endpoints for 12 months after BCG revaccination. Immunologic outcomes have been chosen with the goal of measuring the characteristics and kinetics of human immune responses following BCG vaccination to support the ultimate aim of developing methods to determine the biological relevance of immune responses induced by BCG revaccination and their relevance to protection from tuberculosis (TB). Overall, this study may provide key information on the characteristics and kinetics of immune responses following BCG revaccination in adults and whether these are affected by preclearance with INH treatment of LTBI.