This study examined the role of endogenous opioids in the relation between hostility and cardiovascular stress responsiveness. Forty-six men completed the Cook-Medley Hostility Scale and experienced a laboratory pain stressor once under opioid blockade and once under placebo. Hostility scores were significantly related to the magnitude of change in cardiovascular reactivity/recovery resulting from opioid blockade. Low scorers on the Cynicism subscale displayed increases in heart rate (HR) reactivity under blockade relative to placebo, with reactivity decreases noted in high scorers. Low Hostile Affect scores were similarly associated with impaired diastolic blood pressure recovery under opioid blockade. HR recovery results were somewhat different, with high scorers on Aggressive Responding and the total Cook-Medley displaying improved HR recovery under opioid blockade, with no change noted in low scorers. These data provide preliminary support for the hypothesis that low hostile individuals rely on endogenous opioids for buffering cardiovascular stress responsiveness, but high hostiles do not.