The probability that an uninfected Triatoma infestans would become infected with Trypanosoma cruzi after a single feed on people or dogs seropositive for T. cruzi was estimated in Amama, a rural village in northwest Argentina where transmission had resurged four years earlier. The prevalence of seropositivity for T. cruzi was 34.2% among 225 people tested, and 65.1% among 83 dogs tested. Parasitemia was detected by xenodiagnosis in 29.3% of 41 seropositive persons and in 85.3% of 34 seropositive dogs. Parasitemia decreased with age more sharply in seropositive people than in seropositive dogs. Seropositive humans infected 2.6% (95% confidence interval = 1.6%-3.6%) of 963 third or fourth instar nymphs fed once on them, whereas dogs infected 48.7% (44.7%-52.7%) of 610 nymphs. The probability of bug infection increased significantly with instar and was positively related to molting success. The infectivity to bugs of seropositive dogs was 12 times higher than that of seropositive children, and 100 times higher than that of seropositive adults. The weighted probability of infection of an uninfected bug fed randomly on any dog (0.3082) was about 50 times higher than that of bugs fed on any human (0.0062). Such differences in relative infectivity, combined with the relative host-feeding preference of domiciliary Triatoma infestans for dogs, reinforces the important role of domestic dogs as a risk factor for the domestic transmission of T. cruzi.