OBJECTIVES: Observational studies individually don't shed much light on the association of hepatotoxicity with rifampin and pyrazinamide (RPZ) therapy .The following a priori hypotheses were tested : 1)Every study will have an effect size greater than one; 2) Effect size will vary depending on head count for various risk factors; 3) Intensive monitoring of RPZ therapy reduce hepatotoxicity. In addition to research hypotheses the following research questions were identified: 1) Who are at greater risk of having hepatotoxicity; 2) Is alcohol an effect modifier or a confounder? METHODS: For this research only the observational studies were selected. Electronic searches of MEDLINE (1980 to Aug 2005) were carried out to identify relevant papers. An instrument was devised to assess the quality of the selected studies which measures the quality of the study in range of 1-10.Consistency of the items included in the instrument was described by Cronbach's á(0.7). Review Manager 4.2 (Cochrane Collaboration Center) used to do the meta-analysis. Regression analysis was performed to find relationship between effect size and certain risk factors. RESULTS: The odd ratio of the pooled data is 2.98(2.16-4.11). One of the studies has an effect size of 0.71(0.22-2.27). The odd ratio for risk factors are: liver disease-5.14(1.64-16.10); race-1.85(0.88-3.91); gender-1.66(0.87-3.15); alcohol-1.51(0.82-2.75); age-1.15(0.51-2.62).The odd ratios across the alcoholics and non alcoholics strata are equal. The odd ratio of hepatotoxicity is 0.54(0.21-1.37) among patients who underwent intensive monitoring of RPZ therapy. The R square of the regression for the relationship between effect size, female and non blacks is 0.94 CONCLUSIONS: The meta-analysis of data shows that RPZ users are at higher odd of having hepatotoxicity. The effect size is related to number of female and non black patients included. Female, older, black, and alcoholic are at higher risk. Alcohol is a confounder. Monitoring does reduce the cases of hepatotoxicity.