The Chagas Disease Control Program in São Paulo State, Brazil, now in the entomological surveillance phase, includes a serological examination of individuals residing in domiciliary units infested with vector triatomines infected with Trypanosoma cruzi. From 1990 to 1999, this action included area in which triatomine searches were conducted either as a routine procedure, according to their levels of intra- or peridomiciliary infestation, or at the request of local residents. Among residents of the 1,415 UDs inspected, we collected 5,587 blood samples for serological examination, 87 of which (1.56%) tested positive, seven of which from individuals under 29 years of age. The species most frequently captured were Panstrongylus megistus, Triatoma sordida, and Triatoma tibiamaculata in the adult stage. No association was found between presence of seropositive residents and triatomines infected with Tr. cruzi (OR = 1.498; 0.875 < OR < 2.564, 95% C.I.). Our purpose was to use serological testing to investigate the situation of areas identifiable as being at risk of Chagas disease transmission and to compare the results with extant data about Tr. cruzi infection both in humans and vector triatomines.