In vitro and in vivo studies were performed to clarify the nature of some interactions between Plasmodium berghei sporozoites and rodent host cells. Videomicroscopic observations were made on in vitro interactions between sporozoites and cultured host cells (rodent peritoneal macrophages, W138 human lung fibroblasts, and HepG2 human hepatoma cells). The results showed a diversity of dynamic interactions and sporozoite activities, including active sporozoite penetration, often followed by sporozoite escape, killing of invaded macrophages, phagocytosis of sporozoites by macrophages, and elaboration of a weblike structure by the sporozoite, following its escape from cells. Other studies were performed to examine host cell inflammatory responses to challenge sporozoites in the livers of rats that had been previously immunized with radiation-attenuated sporozoites. The results showed a variety of focal inflammatory infiltrates in the livers of the challenged animals. The relevance of these observations to the problems of sporozoite invasion into natïve and immunized animals is discussed.