The relation between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks) was examined. Plasma monoamine metabolite levels were assayed in 19 flashbackers, of whom 10 experienced a single flashback and 9 exhibited subsequent flashbacks, 18 nonflashbackers with a history of MAP psychosis, 9 subjects with persistent MAP psychosis, and 22 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. They exhibited flashbacks in response to mild psychosocial stressors. There was no significant difference in the number of stressful experiences and having mild psychosocial stressors between the two flashbacker subgroups. Plasma norepinephrine (NE) levels increased with a small increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 19 flashbackers. Of the 19 flashbackers, the 9 with subsequent episodes had markedly increased NE levels and slightly increased 3-MT levels during flashbacks, while the 10 with a single episode displayed small increases in NE and 3-MT levels during flashbacks. The 9 flashbackers with subsequent episodes had a longer duration of imprisonment than the 10 flashbackers with a single episode. Thus, robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may predict subsequent flashbacks. Long-term exposure to distressing situations appears to contribute to susceptibility to subsequent flashbacks.