Somatostatin (SRIF) is a neuroactive peptide that is distributed throughout the nervous system, including the retina. This peptide has been localized to populations of amacrine cells in a variety of vertebrate species. In the rabbit retina, SRIF immunoreactivity is present in a sparse population of medium to large neurons (13.72 microns in diameter, or 147.84 mu 2) in the ganglion cell layer and in a small number of neurons in the inner nuclear layer. These cells display a preferential distribution to the inferior retina, with the highest density near the ventral and ventrolateral retinal margins (11.33 cells/mm2). SRIF-immunoreactive cells have two to five primary processes that arborize in the proximal inner plexiform layer (IPL). These give rise to a plexus of finer processes in the distal IPL. Occasional immunoreactive processes are also present in the outer plexiform layer. In the IPL, these laminar networks are present in all retinal regions. In addition, SRIF-immunoreactive cells often have a fine-caliber axonlike process that eminates from the soma or perisomal region. These processes travel for great distances across the retina in either the nerve fiber layer or in the distal IPL but are never seen to enter the optic nerve head. In addition, the number of SRIF-immunoreactive somata remains unchanged following transection of the optic nerve. Taken together, these data indicate that SRIF-immunoreactive neurons of the rabbit retina are displaced amacrine cells. Furthermore, the sparse distribution of SRIF-immunoreactive somata, the wide-ranging, asymmetric arborization of their cellular processes, and previous pharmacological studies suggest that these neurons mediate a broad modulatory role in retinal function.