The behavior of mice was scored in a multicompartment chamber one hour following intraperitoneal injection of recombinant human interleukin-1 (IL-1). Both IL-1 alpha and IL-1 beta dose-dependently reduced the mean duration for which mice were in contact with novel stimuli without altering measures of locomotor activity, such as movements between the compartments or rears. These behavioral changes resemble those previously observed with prior restraint or intracerebroventricular (ICV) injection of corticotropin-releasing factor (CRF). Effective doses were in the range 0.1-10 ng for IL-1 alpha, and 1-10 ng for IL-1 beta. The reduction in stimulus-contact times induced by 1 ng of IL-1 beta was reversed by prior ICV injection of the CRF antagonist, alpha-helical CRF9-41, suggesting that IL-1 causes secretion of brain CRF which in turn elicits the behavioral changes. These results indicate that peripheral administration of IL-1 alpha or IL-1 beta in low doses can alter behavior. They provide additional evidence that IL-1 administration stimulates brain CRF secretion, and that brain CRF can modulate exploratory behavior, and thus reinforces the concept that IL-1 administration can induce stress.