The invasion process of metacyclic forms of T. cruzi into HeLa cells was investigated with particular emphasis on the role of the cytoskeleton in both cells. The parasite attaches itself to the host-cell membrane and induces the formation of an endocytic vacuole, through which it penetrates into the cell by capping mechanism. The process appears to be reciprocal in that the host cell actively cooperates in the parasite's invasion. A statistically significant reduction in parasitization rates was observed when either the HeLa host cells or the parasite cells were pretreated with Cytochalasin B or Latrunculin B. This effect was even greater when the drugs were added directly to the assay medium. As these two compounds act directly on the actin microfilaments of the cytoskeleton of both T. cruzi and HeLa cells, it would seem that the cytoskeleton of both organisms plays an essential role in the internalization mechanism of the metacyclic forms into nonphagocytic host cells.