Previous investigations showed that interleukin-2 (IL-2) administered in vivo into mice infected with Trypanosoma cruzi reduced levels of parasitemia and increased longevity. Present experiments examined the effect of administration of different doses of IL-2 at different times during infection in mice on parasitemia and histopathology of heart tissue. Two different doses of IL-2 (1,500 or 10,000 U) given at 3 different times during infection were equivalent in reducing parasitemia. All of the IL-2 treated groups of mice had significantly lower numbers of circulating trypomastigotes as compared with controls not receiving this lymphokine. This IL-2 treatment of T. cruzi-infected mice resulted also in lower numbers of pseudocysts in all 4 ventricular regions in the hearts. This was particularly evident in the more severely infected right ventricular wall; however, a similar decrease was not as apparent in the less severely infected left ventricular wall. The IL-2 treated, infected mice showed minimal or no effect in reducing inflammation of myocardial cells. However, the mildest inflammation of ventricular wall tended to occur in mice receiving IL-2 treatment either as a low dose (1,500 U) or a high dose (10,000 U) at 5, 7 and 9 days after infection as compared with mice treated later on. It was concluded that IL-2 treatment of infected mice produced a significant decrease in parasitemia and decreased infection of myocardial cells.