Prophylactic isoniazid therapy is currently recommended for adolescents with positive tuberculin reactions because of the risk of activation of tuberculosis in this age group. Since this drug has been associated with hepatic dysfunction in adults, the present study was undertaken to evaluate its effect on liver function in teen-agers. Accordingly, liver function tests were performed on 178 adolescents prior to and following administration of INH. Abnormalities in SGPT values were encountered in 10% of these patients and occurred in the main within the first 10 weeks of testing, suggesting INH maybe hepatotoxic. However, jaundice was notably absent in the patients with enzyme elevations and prompted a further investigation into the possible effect of INH on bilirubin metabolism. Thus, Sprague-Dawley rats were given four daily injections of INH. These animals manifested increased hepatic bilirubin glucuronyl transferase activity when compared with control rats, supporting the hypothesis that enzymatic induction may be responsible for the absence of jaundice in our adolescent subjects.