The startle reflex protects animals from blows or predatory attacks by quickly stiffening the limbs, body wall and dorsal neck in the brief time period before directed evasive or defensive action can be performed. The acoustic startle reflex in rats and cats is mediated primarily by a small cluster of giant neurons in the ventrocaudal part of the nucleus reticularis pontis caudalis (RPC) of the reticular formation. Activation of these RPC neurons occurs 3-8 ms after the acoustic stimulus reaches the ear. Undetermined neurons of the cochlear nuclei activate RPC via weak monosynaptic and strong disynaptic connections. The strong disynaptic input occurs via neurons of the contralateral ventrolateral pons, including large neurons of the ventrolateral tegmental nucleus that integrate auditory, tactile and vestibular information. RPC giant neurons, in turn, activate hundreds of motoneurons in the brain stem and the length of the spinal cord via large reticulospinal axons near the medial longitudinal fasciculus. To hindlimb motoneurons, monosynaptic connections from the reticulospinal tract are weak, but disynaptic connections via spinal cord interneurons are stronger and show temporal facilitation, like the startle response itself.