BACKGROUND Stress is thought to contribute to both initiation and relapse to drug abuse. However, the mechanisms by which stress influences drug use are unclear. Interestingly, responses to acute administration of stimulant drugs resemble certain neuronal and hormonal responses to acute stress, and there is accumulating evidence that individual variation in the positive reinforcing or euphorigenic effects of a drug is related to individual differences in responsivity to acute stress. METHODS In this study we evaluated relationships between physiological and subjective responses to a stressful task and to an oral dose of d-amphetamine in healthy adult volunteers (N=34). Individuals participated in four experimental sessions; two behavioral sessions involving a stressful task (i.e., public speech) or a non-stressful control task, and two drug sessions involving oral administration of d-amphetamine (20mg) or a placebo. The dependent measures included salivary cortisol, heart rate, mean arterial pressure, and subjective ratings of mood. RESULTS As expected, both stress and d-amphetamine increased cortisol, heart rate and blood pressure. Stress increased negative mood, whereas d-amphetamine induced prototypic stimulant effects and increased ratings of drug liking. Analyses revealed that increased negative mood states after stress were correlated with positive mood after amphetamine. In addition, increased cortisol after stress was correlated with positive mood responses to amphetamine. Finally, there were modest positive correlations between cortisol and heart rate increases after stress and mean arterial pressure after amphetamine. CONCLUSIONS These results support and extend previous observations that responses to acute stress are correlated with certain subjective, hormonal and cardiovascular effects of a stimulant drug.