In this study, we investigated the safety and toxicity of isoniazid (INH) intervention therapy to the patients with latent tuberculosis who were given tumor necrosis factor alpha (TNF alpha) for the treatment of their rheumatologic diseases. In this prospective clinical study, we enrolled 86 patients receiving anti-TNF alpha therapy for their rheumatologic diseases between April 2005 and September 2006. Of all the subjects, 45 had rheumatoid arthritis, 36 had ankylosing spondylitis, and 5 had psoriatic arthritis. In addition to anti-TNF alpha therapy, 60 of the 86 patients were given INH intervention for revealed latent tuberculosis. INH at a dosage of 300 mg daily was given for 9 months. Hepatotoxicity due to the INH therapy was considered when the serum alanine aminotransferase (ALT) and/or aspartate aminotransaminase (AST) levels showed at least threefold increase with respect to their baseline serum levels. Serum ALT and AST levels were measured by enzymatic colorimetric method in fasting peripheral blood samples at 0 (baseline), 1, 2, 3, 6, and 9 months. Of 86 patients, 47 (54.7%) were women (mean age +/- SD, 44.+/- 10.9 years) and 39 (45.3%) were men (38.8 +/- 10.1 years). Except five patients (8.3%), liver toxicity due to the INH therapy was not encountered among the patients, and after temporarily discontinuing the INH therapy of these five subjects, serum transaminase levels returned to the normal ranges. No hepatotoxicity was observed in the non-INH group. However, there was no statistical significance between INH-treated and non-INH-treated group (p=0.317). In addition, none of the 86 patients developed active tuberculosis infection during the treatment period. In conclusion, for those patients who were assigned to the TNF alpha treatment for their rheumatologic disorders and carrying risk for latent tuberculosis, INH intervention therapy was found to be safe and efficacious.