The effects of stress on the serotonergic and noradrenergic projection to the hippocampus were compared in freely moving rats using microdialysis. Stress-induced changes in 5-hydroxytryptamine (5-HT), noradrenaline and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the presence of their respective uptake blockers. Local infusion of tetrodotoxin and replacement of Ca2+ with Cd2+ were used to test dependence on impulse traffic. A 5 min tail pinch or 10 min restraint stress increased 5-HT, 5-HIAA, noradrenaline and DOPAC levels. A subcutaneous saline injection produced an increase in 5-HT and DOPAC but not noradrenaline or 5-HIAA. Although alpha 2 adrenoceptor agonists and antagonists produced changes in the baseline values of noradrenaline and DOPAC, they had little or no effect on stress-induced changes. Both the abolition of impulse traffic and its enhancement by stress had a greater effect on transmitter than on metabolite levels. Although the responses to stress of the noradrenergic and serotonergic pathway showed many similarities, there was evidence for their activation by separate pathways.