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 (> 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 (>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.