ABSTRACTThe large, free‐living amoebae have been widely used as model cells for studying a variety of biological phenomena, including cell motility, nucleocytoplasmic interactions, membrane function, and symbiosis. Results of studies by our group on amoebae as moving cells, as material for micrurgical manipulations, and as hosts for intracellular symbionts are summarized here. In particular, our recent studies of the amoeba as a microcosm, in which spontaneously infecting foreign microbes have become integrated as necessary cell components, are described in some detail. These processes have involved an initial microbial infection, mutual adaptation by the host and symbionts, and development of obligatory symbiosis. Evidence is presented to show that symbiont‐derived macromolecules are involved in the protection of symbionts from digestion, the symbionts have acquired regulatory elements on their chromosomal genes to enhance production of beneficial gene products, and symbionts apparently utilize host‐derived macromolecules to their benefit. These studies involved morphological observations both at light and electron microscopic levels, physiological and genetic studies, production and use of poly‐ and monoclonal antibodies, and molecular‐biological approaches including gene cloning and sequencing. It is shown that amoebae are uniquely suited as model cells with which to study these