Certain crosses of common bean (Phaseolus vulgaris) result in temperature-dependent hybrid weakness associated with a severe root phenotype. This is controlled by the interaction of the root- and shoot-expressed semidominant alleles dosage-dependent lethal 1 (DL(1)) and DL(2), which communicate via long-distance signaling. Previously, apparent reciprocal effects on root growth and the restoration of normal root growth by exogenous sucrose led to the hypothesis that the dosage-dependent lethal (DL) system may control root-shoot carbon partitioning. Here, recombinant inbred lines were used to map the DL loci and physiological and biochemical analysis, including metabolite profiling, was used to gain new insights into the signaling interaction and the root phenotype. It is shown that the DL system does not control root-shoot carbon partitioning and that roots are unlikely to die from carbon starvation. Instead, root death likely occurs by defense-related programmed cell death, as indicated by salicylic acid accumulation. DL(2)-expressing cotyledons supply a potent inhibitory signal that is sufficient to cause such death in DL(1)-expressing roots. These data implicate the DL system in defense-related signaling and provide support for the recent hypothesis of defense-related autoimmunity as a potential isolating mechanism in plant speciation, in particular, setting a precedence for the potential roles of long-distance signaling and temperature dependence.