Systemic administration of interleukin-1beta (IL-1beta) promoted behavioral changes in an open-field exploratory test. In particular, while the cytokine suppressed locomotor activities, these behaviors were not particularly sensitive to dosage differences. In contrast, dose-dependent biphasic variations that varied over time were evident with respect to the exploration of a novel container. Within this paradigm, the behavioral changes did not appear to be related to neophobia. In addition, despite the marked effects of IL-1beta on exploratory and locomotor behaviors, habituation/exploration in a free-running spontaneous alternation task was unaffected by the cytokine. In addition to the behavioral variations, IL-1beta dose-dependently increased plasma ACTH and corticosterone concentrations, and also induced several central monoamine alterations. In particular, IL-1beta increased the utilization of norepinephrine (NE) within the paraventricular nucleus, arcuate nucleus/median eminence, locus coeruleus, and prefrontal cortex, while the turnover of dopamine (DA) was evident in the arcuate nucleus/median eminence. It is suggested that although systemic IL-1beta treatment induces some stress-like effects, the profile of central neurochemical changes induced by the cytokine can be distinguished from psychological or processive types of stressors.