Mouse peritoneal elicited macrophages cultured on coverslips were infected with Trypanosoma cruzi trypomastigotes from both the F strain and Y strain obtained either from tissue culture or from the bloodstream of infected mice. Both the Y strain and F parasites obtained from tissue culture were interiorized by macrophages at a much higher rate than bloodstream trypomastigotes. Tissue culture parasites incubated with normal mouse serum, mouse plasma obtained at the 7th day after infection, or specific hyperimmune serum at subagglutinating concentration, behaved essentially as non-opsonized parasites. Ultrastructural differences were seen at the early interaction phase between macrophages and trypimastigotes from both sources. After 30 minutes, tissue culture trypomastigotes were located in clusters at the area of contact with macrophages. While bloodstream trypomastigotes, at 3 hours post-infection were most frequently enclosed in a loose phagocytic vacuole, tissue culture trypomastigotes were enclosed in single tight vacuoles. Both tissue culture and bloodstream trypomastigotes of the Y strain multiplied within macrophages; F strain bloodstream trypomastigotes did not develop within the host cells, while tissue culture trypomastigotes multiplied.