Cytokine-specific alterations of monoamine activity were evident in the hypothalamus, hippocampus and prefrontal cortex 2 h following peripheral administration of recombinant interleukin (IL)-1 beta, IL-2 and IL-6 (200 ng, i.p.) in male, BALB/c mice. IL-1 induced the broadest range of neurochemical changes, affecting central norepinephrine (NE), serotonin (5-HT) and dopamine (DA) activity. In particular, IL-1 enhanced NE turnover in the hypothalamus and hippocampus, 5-HT turnover in the hippocampus and prefrontal cortex (owing to increased utilization and reduced content of the transmitters in these brain regions), and enhanced DA utilization in the prefrontal cortex. IL-6 increased 5-HT and DA activity in the hippocampus and prefrontal cortex in a manner similar to IL-1, but failed to affect central NE activity. Moreover, IL-2 increased hypothalamic NE turnover (reflecting a profound increase in NE utilization) and enhanced DA turnover in the prefrontal cortex, but did not influence central 5-HT activity. Hence, these cytokines differentially altered neurochemical activity in brain regions that mediate neuroimmune interactions and that are influenced by physical and psychological stressors. In addition to the neurochemical changes, plasma corticosterone concentrations were profoundly enhanced in IL-1-treated animals, but not significantly altered by IL-2 or IL-6 treatment. The IL-1-induced corticosterone elevations did not significantly correlate with alterations of hypothalamic NE activity.