The effects of repeated amphetamine administration on stress-induced dopamine release in the ventral striatum were examined in male Wistar rats treated with D-amphetamine (1.5 mg/kg; i.p./injection) or saline at 12 h intervals for 14 days. After 12 h as well as 7 days of amphetamine withdrawal, dopamine release was monitored by transverse microdialysis under basal conditions and during exposure to 60 min of restraint stress. Basal dopamine release was significantly suppressed relative to saline-pretreated controls after both 12 h and 7 days of amphetamine withdrawal. In control rats, restraint stress resulted in significantly increased dopamine efflux. In contrast, exposure to this stressor was associated with a significant suppression of dopamine release in rats chronically exposed to amphetamine. This effect was observed at both post-amphetamine test points. The results suggest that chronic amphetamine impairs the dopaminergic response to stress and that this dopaminergic deficit may play a role in stress-induced drug-seeking behavior and relapse.