Interrupting the transmission of Chagas' disease using insecticide-treated materials could be a cost-effective option, particularly for sylvatic vectors, which enter houses at night. A randomized trial was undertaken that included all houses in two communities in regions endemic for this disease, one in Venezuela (50 houses) and one in Colombia (47 houses). After a baseline study (including a short questionnaire survey, entomologic assessment, and Chagas' disease serology), each household was randomly allocated to either the intervention group, which used pyrethroid-impregnated bed nets, or the control group, which used unimpregnated bed nets. Serologic analysis of children in the baseline study showed active transmission of Chagas' disease in the Venezuelan community (10.7% of 103 children were positive), but none in the Colombian community (0% of 100 children were positive). Vectors were sylvatic and bugs entered the houses at night in both communities. The efficacy of pyrethroids against triatomine vectors was tested in Venezuela by exposing Rhodnius prolixus to lambdacyhalothrin-impregnated fabrics and in Colombia by residual house spraying with deltamethrin. This randomized trial showed that in both countries users of impregnated bed nets were well protected from vector bites (immediate benefit). The long-term effect on the community was high vector mortality. In Venezuela, all 62 vectors detected (mainly R. robustus) died within 72 hours of contact with impregnated bed nets. In houses that used unimpregnated nets, only 24.5% (13 of 53) of the vectors died (P < 0.001). The vectors most likely came from infested palm trees and they maintained transmission of the disease in this community (28.1% of 629 R. robustus were positive for Trypanosoma cruzi). Bioassays showed that the mortality rate of R. prolixus was 100% on lambda-cyhalothrin-impregnated materials. In addition, in Colombia (the main vector was R. prolixus), the effect of repellent on vectors (driving them away from impregnated nets) was significant. Thus, users of impregnated bed nets are well protected from transmission of Chagas' disease, and vector reduction or elimination can potentially be achieved in areas infested with R. prolixus and R. robustus.