The toxicity of isoniazid chemoprophylaxis was assessed in 83 health care workers (HCWs) receiving a 6-month course, in whom clinical toxicity and liver function were monitored. Thirty-four HCWs (41%) developed an adverse event; in 26 (76%), toxicity was sufficiently severe to require cessation of treatment. Of the total, liver function test abnormalities (serum alanine transaminase levels more than two times normal) were evident in 14 subjects, with 8 requiring cessation of therapy. Other symptoms reported included malaise, nausea with associated anorexia, arthralgia, and rash. Mean time to development of symptoms was 3 weeks (range, 0.5-6 weeks), with the mean age of those with toxicity not differing significantly from those without (38 vs. 39 years). The high rate of toxicity seen in this study is sufficiently notable that we advocate the use of monthly liver function testing and frequent review in those receiving isoniazid prophylactic therapy.