Under experimental conditions, the course of the infection and the response to the reinfection by Trypanosoma rangeli in mice and Didelphis marsupialis, are studied. During the initial infection the mice show a relatively low parasitaemia and a short patent period. A scanty parasitaemia level of four days length, was observed following the first reinfection, being the mice resistant to new reinfections by T. rangeli. In opossums a lower parasitaemia and a longer patent period than that detected in mice, were observed during the initial infection. The response to reinfections in this mammal, was similar to that observed in mice. After reinfection with T. rangeli, haemagglutinant antibodies in immune-sera of both mice and opossums, were detected. The possible immune-response at the site of deposition against the metacyclic-forms of T. rangeli, and the action of circulating antibodies against the blood forms of the parasite, are speculated to explain the resistance of mice and opossums to the reinfection by T. rangeli.