The postulate that rapid acetylation (AC) is a risk factor in INH hepatitis has been examined in a prospective study of 66 patients receiving preventive INH (300 mg daily) for up to 9 mth. A careful history (including other drug therapy and previous hepatic dysfunction), baseline liver function tests and AC status were obtained prior to INH therapy. Patients were deemed to have evidence of liver damage from INH if the following conditions were met: normal baseline SGOT, abnormal SGOT > 60 KU on 2 or more occasions (at least 2 wk apart), and SGOT greater than 4 x mean baseline value on one occasion. Seven patients (10.6%) had evidence of liver damage and are analyzed below with respect to age and inactivation index (I.I). Furthermore, AC status was repeated after 3 mth therapy in half of the patients and showed no induction of the acetylation enzyme system. The mean I.I for those with hepatitis was 3.20 (S.E. ± 1.83) while the mean I.I for the nonhepatitis patients was 6.2 (S.E. ± .84). Chi square analysis for incidence of hepatitis (with respect to I.I below or above 3.0) disproves the postulate that rapid AC is a risk factor for INH hepatotoxicity (p < .05).