Background and Aims. Even though it has been reported that chronic immune activation associated with intestinal helminthic infections results in a predominant IgE response, specific IgE antibodies that are also interleukin 4 (IL-4) dependent have been reported in tuberculosis patients; however, this fact has not been widely reported. This study was aimed at investigating the levels of circulating IgE in Warao (an indigenous population) of the Orinoco river delta, an area isolated from contact with the tubercle bacillus for millennia until the mid-1960s as compared to Creole (nonindigenous population). Methods. A total of 294 individuals were studied, 161 Warao and 136 Creole. Patient group was comprised of 86 Warao patients (WP) and 60 Creole patients (CP). Control group was comprised of 75 Warao controls (WC) and 76 Creole controls (CC). Total serum IgE and IgE and IgG4 reactivities to M. tuberculosis antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Results. Levels of total serum IgE were significantly elevated in WP (13002.0 11200.0 IU/mL) and WC (2763.5 2596.2 IU/mL) than in CP (385.9 155.1 IU/mL) and CC (356.6 157.5 IU/mL) ( p !0.0001). Anti-PPD and anti-H37Rv IgE were significantly higher in WP (0.240 0.145 and 0.230 0.155) than in CP (0.127 0.152 and 0.97 0.103, respectively) and also between WC (0.240 0.273 and 0.147 0.158) and CC (0.115 0.136 and 0.43 0.46, respectively) ( p !0.0001). Anti-PPD and anti- H37Rv IgG4 did not show differences among groups; however, anti-H37Rv IgG4 was affected by anti-TB treatment, which could be predictive of treatment outcome. Conclusions. The findings suggest that for the Warao population there is an intrinsic propensity to produce a high IgE response, which could be incompatible with the protective response to M. tuberculosis.2012 IMSS. Published by Elsevier Inc.