Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed gestationally by chronic mild stress (CMS, a variable schedule of different stressors) or dexamethasone (DEX, a synthetic glucocorticoid, i.e., a pharmacological stressor) was tested for reactivity by testing their acoustic startle response (ASR). Two subsets of offspring were tested. One was experimentally naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring that had been blood sampled 3 months previously. In conclusion, similarity of the effects of maternal gestational exposure to a regular stress schedule and of exposure to a synthetic glucocorticoid suggests that maternal glucocorticoids may be a determining factor for changes in the regulatory mechanisms of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very beginning of life affect the individual's sensitivity towards experiences in life after birth. The prenatal environment may thus form part of the explanation of the considerable individual variation in the development of psychopathology.