Brain interleukin-1 (IL-1) plays a key role in mediating the neural, endocrine, and behavioral consequences of injury and infection. Recent evidence indicates that brain IL-1 may also be important in producing endocrine and neurochemical responses to stressors. The present experiment sought to determine whether intracerebroventricular (i.c.v.) administration of an interleukin-1 receptor antagonist (IL-1ra) would block behavioral effects of a stressor. I.c.v. application of hrIL-1ra before inescapable shock blocked the subsequent interference with escape learning and enhancement of fear conditioning normally produced by this treatment.