The effects of application of five different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the striatum and hippocampus were compared using in vivo microdialysis. Forced swimming for 30 min elevated extracellular 5-hydroxytryptamine to 90% above basal levels and reduced 5-hydroxyindoleacetic acid to 45% of basal levels in the striatum during the swim session. In contrast, hippocampal 5-hydroxytryptamine was not altered significantly by forced swimming but 5-hydroxyindoleacetic acid levels were reduced to 60% of basal levels. Tail pinch for 5 min elevated 5-hydroxytryptamine to 55% above basal levels in striatum and to 35% above basal levels in hippocampus. Tail pinch had no effect on 5-hydroxyindoleacetic acid in either brain region. In contrast to forced swimming and the tail pinch, the other three stressors, immobilization stress for 100 min, exposure to a cold environment (4 degrees C) for 2 h, and forced motor activity on a rotarod for 30 min, failed to alter extracellular 5-hydroxytryptamine in either the striatum or the hippocampus. All five stressors increased plasma corticosterone levels: tail pinch, 246%; cold stress, 432%; immobilization, 870%; forced motor activity, 1030%; and forced swimming, 1530%. These results suggest that individual stressors produce different effects on extracellular 5-hydroxytryptamine in different brain regions. In addition, there does not appear to be a relationship between the effects of stressors on the 5-hydroxytryptamine system and the magnitude of their ability to activate the hypothalamic-pituitary-adrenal axis.