A challenging question that continues to plague the field of addiction is why some individuals are more vulnerable for substance use disorders than others. Several important risk factors for substance abuse have been identified in clinical studies, including trait impulsivity and environmental stress. However, the neurobiological mechanisms that underlie the relationships remain poorly understood. The purpose of this study was to examine associations among impulsivity, stress, and striatal dopamine (DA) responses to amphetamine (AMPH) in humans. Forty healthy M, F adults, ages 18–29 years, completed self-report measures of trait impulsivity, life events stress, and perceived stress. Subjects subsequently underwent two consecutive 90-min positron emission tomography (PET) studies with high specific activity [11C]raclopride. The first scan was preceded by an intravenous injection of saline; the second was preceded by 0.3 mg/kg AMPH. Findings showed that high impulsivity was associated with blunted right ventral striatal DA release. However, effects were modified by a significant interaction with life events stress. Dopamine release was greater in low vs. high impulsivity subjects under conditions of low or moderate stress. Under conditions of high stress, both groups had low DA release. Subjects with high impulsivity reported more pleasant effects with AMPH than subjects with low impulsivity. In contrast, stress was negatively associated with pleasant drug effects. No associations were observed between impulsivity or stress and cortisol responses to AMPH. The findings are consistent with notions that blunted DA responses represent an endophenotype for substance use disorders.