We studied the association between human incidence of Trypanosoma cruzi infection and household infestation density of Panstrongylus megistus in Castro Alves, Bahia, Brazil. During a 9-year period, 19 persons seroconverted; 17 were children, 17 lived in nonplastered houses, and 13 lived in houses infested with triatomines. Although 6 seroconverting persons lived in houses where triatomines could not be found, the risk of seroconversion was significantly greater in infested houses and 16 times greater in densely infested houses (greater than 15 bugs/person-hour of search). The highest rate of seroconversion (6/100 person-years exposure) occurred in houses containing the greatest number of bugs infected with T. cruzi (greater than 6 infected bugs/person-hour). These observations suggest that vector control measures could have a dramatic impact on transmission of T. cruzi by P. megistus.