Central administration of 15 ng interleukin (IL)-1β in the rat significantly enhanced conditioned fear memory assessed by a passive avoidance task, when retested at 24 and 48 h post-training. Pain threshold was unaffected by 15 ng IL-1β administration. IL-1β treatment also increased serum corticosterone. This increase in serum corticosterone was further enhanced in rats given both IL-1β and footshock. Furthermore, the glucocorticoid receptor antagonist mifepristone blocked IL-1β-induced elevation in corticosterone and also attenuated the enhanced conditioned fear memory. Central administration of IL-1β significantly increased prostaglandin E2 and decreased the anti-inflammatory cytokine IL-10 release from whole blood cultures; therefore this treatment appears to be effective in inducing an inflammatory response in both the periphery and the brain. The present study confirms that IL-1β can enhance conditioned fear memory, an effect which is correlated with changes in glucocorticoid function. This facilitation of defensive behaviour could reflect adaptive responses which may enhance survival during sickness.