The temporal and dose-related behavioral and striatal monoamine response to amphetamine (AMPH) was examined using in vivo microdialysis in freely moving rats. Extracellular dopamine (DA), serotonin (5-HT), and their metabolites were monitored concomitant with detailed characterization of the locomotor and stereotypy profiles. Consistent with previous results, AMPH (0.5-5.0 mg/kg) induced a rapid dose-dependent increase in DA concentration and decrease in the concentrations of the DA metabolites, DOPAC and HVA. DA and its metabolites exhibited contrasting temporal and dose-related patterns, suggesting that the decline in DA metabolites is functionally dissociated from the AMPH-enhanced DA release. In addition, AMPH at doses of 2.0 mg/kg and greater significantly increased extracellular concentrations of 5-HT, which, in contrast to the changes in dopamine, persisted for only 20-40 min. Comparisons of concentrations of DA and 5-HT for individual animals revealed significant correlations both during baseline and drug response, suggesting a possible functional interdependence between dopaminergic and serotonergic activity in striatum. Dose-response comparisons revealed a significant relationship between AMPH-induced increases in behavioral perseveration and the magnitude and duration of the DA release. However, the temporal patterns of the neurotransmitter response and individual components of stereotypy were not parallel, suggesting that the presence of stereotypies is not associated simply with quantitative differences in striatal DA release. By contrast, some features of the behavioral response were significantly correlated with AMPH-induced changes in striatal 5-HT concentrations. Our results suggest that the behavioral response to AMPH may be influenced by the interaction between levels of DA and 5-HT release, as well as by the state of their respective receptors.