The long-term goal of the proposed research is to achieve molecular understanding of the interactions between intracellular parasites and their hosts that determine (a) whether or not the parasite will be phagocytosed and (b) whether the ingested parasite will be killed or whether it will multiply and kill its host. The research will be carried out with mouse fibroblasts (L cells) and mouse macrophages as host cells, and bacteria of the genus Chlamydia (etiologic agents of psittacosis and trachoma) as parasites. The general working hypothesis will be that the outcome of host-parasite encounters depends on reactions between the surface of the parasite and the surface of the host cell and of its membrane-bound organelles, the phagosomes and lysomsomes in particular. In pursuit of these long-term goals, the following questions will be asked. Whenever possible, parallel studies will be made with L cells and mouse peritoneal macrophages as the host cells. (1) Are there differences in the way host cells recognize and ingest representative strains of C. psittaci and C. trachomatis? (2) Why do host-cell lysosomes fuse with phagosomes enclosing noninfectious chlaymdiae, but do not fuse with phagosomes enclosing infectious ones? (3) Are the biochemical changes accompanying phagocytosis of chlamydiae by nonprofessional phagocytes (L cells) the same as those for professional phagocytes (mouse macrophages)? Do such changes play a role in the intracellular killing of chlamydiae?