The great variability in the clinical presentation of Chagas disease may depend in part in the genetic variability of Trypanosoma cruzi populations. Aim: To compare prepatent period, parasitemia, mortality and histological lesions in mice infected with two populations of Trypanosoma cruzi isolated in Chile. Material and methods: Two Trypanosoma cruzi populations, isolated from Chilean Triatomides and genetically characterized by kinetoplast restriction fragment DNA profiles, were compared. Two groups of 40 Balb/c mice were studied. Each mouse was inoculated with 10(4) trypomastigotes, of the V-121 and sp COMB 2 Trypanosoma cruzi populations. The prepatent period, parasitemia, mortality and histopathological lesions, at different evolutionary stages of infection were registered during 32 days. Results: Prepatency and mortality were similar in both groups of mice. However, parasitemia was significantly greater in mice inoculated with V-121 than those inoculated with sp COMB 2. Amastigote pseudocysts and inflammation were present only in skeletal muscle and myocardium in both groups of mice. The intensity of tissue involvement was associated to the level of parasitemia, therefore it was greater in mice inoculated with V-121 population. Conclusions: V-121 population of Trypanosoma cruzi caused a greater parasitemia than COMB 2, in inoculated mice