Peptidergic fibers in the globus pallidus of the monkey appear in the morphological form referred to as woolly fibers. These fibers are composed of a dense plexus of thin beaded axons which ensheath an unstained central core. Such structures are not confined to the globus pallidus, but are also present in the bed nucleus of the stria terminalis, the hypothalamus, the dorsal part of the amygdala, and ventrally in the basal forebrain. The present study describes the relationship between projections from the rostral and ventral striatum and the enkephalin- and substance P-positive woolly fibers. Following injections of either tritiated amino acids or the lectin Phaseolus vulgaris-leucoagglutinin in the ventral striatum, anterogradely labeled fibers and terminals in the forebrain were visualized simultaneously with enkephalin- or substance P immunoreactivity in the same tissue section in order to determine: (i) the extent to which the woolly fiber distribution represents striatal output systems; (ii) whether woolly fibers can be considered as a marker for the entire striatal forebrain projection; and (iii) whether enkephalin and substance P are involved differentially in distinct ventral striatopallidal pathways. Phaseolus vulgaris-leucoagglutinin labeling is seen in the globus pallidus and adjacent structures either as single, beaded fibers or in a profile strikingly similar to that of woolly fibers. In tissue sections treated for a double immunohistochemical protocol, following which the Phaseolus vulgaris-leucoagglutinin-immunoreactive fibers turn black and the peptidergic woolly fibers brown; many of the lectin-positive fibers are seen to enter the peptide-positive woolly fiber plexus. Likewise, following the injections with tritiated amino acids in the ventral striatum, coarse structures that have dimensions resembling those of the woolly fibers are identified. In sections immunohistochemically stained and subsequently treated for autoradiography, peptide-positive woolly fibers can be identified underlying the silver grains. In sections stained for both peptide immunoreactivity and tracer substances, enkephalin or substance P-positive woolly fibers are present in all pallidal regions that receive ventral striatal input. However, the ventral striatum also sends fibers to the hypothalamus, bed nucleus of the stria terminalis, the dorsal part of the amygdala, the septum, the preoptic area, and other areas of the basal forebrain. In these nuclei the peptide-positive woolly fiber distribution is less extensive than the terminal labeling. The distribution of substance P-positive fibers in the subcommissural pallidal region is more limited than the distribution of enkephalinergic fibers.(ABSTRACT TRUNCATED AT 400 WORDS)