Field populations of Triatoma infestans Klug were collected during 2002 from four villages in northern Argentina (El Chorro, La Toma, El Sauzal, and Salvador Mazza), after application of deltamethrin and other pyrethroids was ineffective. High levels of resistance to the pyrethroid insecticides deltamethrin, β-cypermethrin, β-cyfluthrin, and lambda-cyhalothrin were detected in all of the evaluated populations. The resistance ratio to pyrethroids determined by topical application ranged from 50.5 (deltamethrin, El Sauzal) to 667.6 (β-cyfluthrin, Salvador Mazza). None of the pyrethroid-resistant insects was resistant to the organophosphorus insecticide fenitrothion. Topical application of piperonyl butoxide to the most deltamethrin-resistant population (Salvador Mazza) led to slight reduction in levels of resistance. Activity of P450 monooxygenase, measured in individual insects through ethoxycoumarine-O-deethylase, showed a slight but noticeable difference in the distribution of activities between susceptible and resistant populations. The total percentage of insects below 0.48 pmol of 7-OH coumarine/min/insect was 36.4 for Salvador Mazza population and 64.3 pmol of 7-OH coumarine/min/insect for CIPEIN strain. Whereas a low level of resistance to deltamethrin was previously related to monooxygenase activity in T. infestans, the high levels of resistance shown by these populations seem to involve monooxygenase in combination with other resistance mechanisms, for example, insensitivity of nervous membrane. Research on T. infestans resistance is in progress to improve Chagas vector control programs in Latin America and to implement resistance management strategies.