Laboratory studies indicate that the life-span of inbred rodent strains is inversely related to the intensity of their behavioral and neuroendocrine responses to stressful stimuli. In the brain, a shorter life-span is associated with accelerated age-dependent degenerative changes in specific stress-responsive neuronal systems. The evidence suggests a possible genetic linkage between the intensity of the stress response, the rate of age-dependent neurodegeneration and the individual's life expectancy. It is proposed that inherent hyper-reactivity to stressors is genetically linked to a shorter life-span and to accelerated age-dependent neurodegeneration. Several experimental approaches to test 'this stress-longevity-neurodegeneration linkage hypothesis' are outlined.