One of the recommended treatments for latent tuberculosis infection (LTBI) is a 9-month regimen of isoniazid (INH); a 2-month regimen of rifampin (RIF) and pyrazinamide (PZA) is an alternative in some instances. In September 2000, a man in New York died of hepatitis after 5 weeks of RIF-PZA, and in December, a woman in Georgia was admitted to a hospital because of hepatitis after 7 weeks of this regimen. This report summarizes the findings of the investigations of these incidents, which underscore the need for clinical monitoring for adverse effects in all patients receiving treatment for LTBI.