The role of endogenous opioids in the cardiovascular response to mental stress was investigated in two controlled studies. In the first, cardiovascular, hormonal and psychological measures were made in a group of subjects before, during and after presentation of either a mental stress task or a non-stressful control task in the presence of naloxone (8 mg), an opiate antagonist, or an equal volume of saline. The study was carried out in random order and single(subject)-blind. Naloxone specifically enhanced the heart rate response to the stressful task but had no effect on blood pressure, plasma epinephrine or norepinephrine, or feelings of anxiety. Naloxone increased plasma cortisol and ACTH in both stressful and control tasks. A second, double-blind, study replicated the effect on heart rate. An endogenous opioid mechanism thus appears to inhibit the cardiovascular response to stress.