The objective was to test whether theoretical variables predict adherence to treatment for latent tuberculosis infection in high-risk Latino adolescents. 286 Latino adolescents, age 13-18 years, were recruited from 10 middle/high schools in San Diego County, San Diego, USA. Participants completed a baseline interview and up to 9 monthly interviews. The cumulative number of pills consumed in 9 months was regressed on 16 independent variables, entered hierarchically in seven blocks. The final model accounted for 25% of the variance in adherence to isoniazid (INH), F (16, 230)=4.69, p<0.001. Adherence counseling (+), age (-), grades (+), being bicultural (+), and risk behaviors (-) were significantly related to adherence. Learning theories presume that adherence to medical regimens requires social support and freedom from physical and social barriers. Results support these theories. Future studies should explore additional precepts in order to identify additional predictors and to maximize adherence to INH among Latino adolescents and other high-risk populations. Doing so should decrease the risk of active TB among high-risk racial/ethnic and foreign-born populations.