The present study examined the effect of anti-inflammatory agents on the behavioral and plasma cortisol responses of guinea pig pups during isolation in a novel environment. In Experiment 1, intracerebroventricular (ICV) administration of interleukin-10 (IL-10), across a range of doses, significantly reduced passive behaviors of isolated pups. In Experiment 2, neither ICV IL-10 nor alpha-melanocyte stimulating hormone affected the plasma cortisol response to the separation procedure. These results provide further evidence that the passive behaviors of isolated guinea pig pups are mediated by proinflammatory cytokines and indicate that cytokines do not affect behavior indirectly by means of an action on hypothalamic-pituitary-adrenal activity.