During February 12-August 24, 2001, a total of 21 cases of liver injury associated with a 2-month rifampin-pyrazinamide (RIF-PZA) regimen for the treatment of latent tuberculosis infection (LTBI) was reported to CDC. These 21 cases are in addition to two previously reported RIF-PZA-associated cases. Cases of liver injury have occurred each year since 1999. CDC also received reports of 10 cases associated with other LTBI treatment regimens; however, risk for liver injury cannot be compared among treatment regimens in part because the number of patients treated for LTBI with each treatment regimen is unknown. This report provides preliminary information about the 21 cases associated with RIF-PZA and the revised recommendations on selecting appropriate LTBI therapy for patients and monitoring the use of RIF-PZA to treat LTBI. In most instances, the 9-month isoniazid (INH) regimen is preferred for the treatment of patients with LTBI. RIF-PZA may be used in selected cases and requires more intensive clinical and laboratory monitoring than previously recommended.