Microorganisms interact frequently with each other and with higher organisms. This contact and communication takes place at the molecular level. Microbial interactions with eukaryotes can be pathogenic or mutualistic. One of the best-studied symbioses is the complex interaction between nitrogen-fixing soil bacteria, termed rhizobia, and legumes. This symbiosis culminates in the elaboration of a new organ, the root nodule. Many of the molecular signals exchanged between the host plant and the invading rhizobia have been deduced, but there is still much that remains to be discovered. The molecular determinant of host range at the genus level of the plant host has been determined to be lipochitooligomers called Nod factors. The molecular determinants of host range at the species and cultivar level are less well-defined. Part of my work has been to identify and characterize accessory plasmids that disrupt the normal progression of symbiosis between legumes of the genus Medicago and their rhizobial symbiont, Sinorhizobium meliloti. A cre--loxP-based system capable of making large, defined deletions was developed for the analysis of these plasmids. This system is also being employed to cure the laboratory strain, S. meliloti Rm1021 of its two megaplasmids-a loss of nearly half of its genome. I have also done work to determine whether locally-collected sinorhizobia are native, invasive, or native with symbiosis genes acquired horizontally from invasive sinorhizobia. Finally, I have studied Sinorhizobium meliloti as a host by identifying an outer membrane porin that several bacteriophages use to adsorb to the S. meliloti cell surface.