The objective of this exploratory pilot study was to examine autonomic reactivity and hypothalamic pituitary adrenal axis dysregulation in spouses of highly exposed survivors of the 1995 Oklahoma City bombing.This study compared psychiatric diagnoses and biological stress markers (physiological reactivity and cortisol measures) in spouses of bombing survivors and matched community participants. Spouses were recruited through bombing survivors who participated in prior studies. Individuals with medical illnesses and those taking psychotropic medications that would confound biological stress measures were excluded. The final sample included 15 spouses and 15 community participants. The primary outcome measures were psychiatric diagnoses assessed with the Diagnostic Interview Schedule for DSM-IV (DIS-IV). Biological stress markers were physiological reactivity and recovery in heart rate and blood pressure responses to a trauma interview and cortisol (morning, afternoon, and diurnal variation).Compared to the community participants, spouses evidenced greater reactivity in heart rate, systolic blood pressure, and diastolic blood pressure; delayed recovery in systolic blood pressure; and higher afternoon salivary cortisol.The results support the need for further research in this area to clarify post-disaster effects on biological stress measures in the spouses of survivors and the potential significance of these effects and to address the needs of this important population which may be overlooked in recovery efforts.