Triatomine insects (Hemiptera: Reduviidae), commonly known as kissing bugs, are a potential health problem in the southwestern United States as possible vectors of Trypanosoma cruzi, the causative agent of Chagas disease. Although this disease has been traditionally restricted to Latin America, a small number of vector-transmitted autochthonous US cases have been reported. Because triatomine bugs and infected mammalian reservoirs are plentiful in southern Arizona, we collected triatomines inside or around human houses in Tucson and analyzed the insects using molecular techniques to determine whether they were infected with T. cruzi. We found that 41.5% of collected bugs (n = 164) were infected with T. cruzi, and that 63% of the collection sites (n = 22) yielded >or=1 infected specimens. Although many factors may contribute to the lack of reported cases in Arizona, these results indicate that the risk for infection in this region may be higher than previously thought.