Giant fibers are large reticular interneurons that mediate excitatory input from the Mauthner cells to pectoral-fin motoneurons. The present study revealed extensive giant-fiber projections to central targets other than the pectoral-fin motoneurons. Physiologically identified giant fibers were filled intracellularly with Lucifer Yellow. The presence of numerous dendrites suggests that there may be significant integration of non-Mauthner inputs in the giant-fiber cell body. The axon decussates and then bifurcates to form a descending process, that innervates pectoral-fin motoneurons, and an ascending process with collaterals that terminate in the rostral trigeminal, rostral facial and, in some cases, oculomotor and trochlear motor nuclei. The projections are consistent with a role for the giant fibers as mediators of all the cranial components of the Mauthner-initiated startle response. There are also extensive projections to cells near the Mauthner cell and to the medial reticular formation. The latter projections may participate in longer-latency components of the Mauthner-initiated startle response, or they may constitute part of a general arousal pathway. The morphology of giant fibers suggests that they are homologous to cranial relay neurons in the goldfish and T reticular interneurons in zebrafish larvae. Non-Mauthner inputs to giant fibers may participate in non-Mauthner startle responses and contribute to the variability of Mauthner-mediated startle responses.