During military operations, soldiers may be exposed to mixtures of chemicals and to physical, emotional and psychological stress factors, which all may influence efficacy of any treatment, including the nerve agent pretreatment regimen. The purpose of this study was therefore to investigate the influence of chronic intermittent, variable, unpredictable and uncontrollable stress conditions on the side effects and therapeutic efficacy of the combination of physostigmine (0.025 mg/kg/h) and scopolamine (0.018 mg/kg/h) as a pretreatment against 2 x LD50 soman intoxication in guinea pigs. Stress during pretreatment led to an increase of motor activity and an increase of power in the EEG delta2 frequency band. After chronic stress, exposure of pretreated animals to 2 x LD50 soman resulted in more severe intoxication symptoms, a more persistent effect on the startle response, and considerable more severe and persistent effects on the EEG power-spectrum, indicating irreversible brain damage.