Development of the Rhizobium-legume symbiosis is controlled by the host plant, although the underlying mechanisms have remained obscure. A mutant in the annual legume Medicago truncatula exhibits an increase of more than an order of magnitude in the number of persistent rhizobial infections. Physiological and genetic analyses indicate that this same mutation confers insensitivity to the plant hormone ethylene for multiple aspects of plant development, including nodulation. These data support the hypothesis that ethylene is a component of the signaling pathway controlling rhizobial infection of legumes.