The distribution of somatostatin binding sites was studied in the pons and medulla oblongata of three human fetuses (gestional ages 26, 28 and 30 weeks). The study was carried out by in vitro quantitative autoradiography using either [125I-Tyr0,D-Trp8]somatostatin-14 or [125I-Tyr11]somatostatin-14 as radioligands. Somatostatin binding sites were observed in a number of nuclei subserving sensory, motor or integrative functions within the pons and medulla. In addition, discrete tracts also contained significant amounts of binding sites. Among structures involved in sensory processes, a high density of binding sites (40-60 fmol/ mg wet tissue) was measured in the dorsal cochlear nucleus and in the nucleus tractus spinalis trigemini caudalis. Moderate to high levels of binding sites (30-40 fmol/mg wet tissue) were detected in the other sensory cranial nerve nuclei. A moderate density of sites (15-30 fmol/mg wet tissue) was measured in most motor nuclei, the highest concentrations being observed in the dorsal motor nucleus of the vagus nerve, the facial nucleus, the hypoglossal nucleus and the nucleus ambiguus. The griseum pontis and the nucleus corporis pontobulbaris contained very high (> 60 fmol/mg wet tissue) and high concentrations of somatostatin binding sites, respectively, while the other relay nuclei contained low to moderate levels of binding. In monoaminergic nuclei, very high and moderate to high concentrations of somatostatin binding sites were measured in the nucleus locus coeruleus and in its dorsal subnucleus, respectively. Moderate densities of sites were detected in the ventral subnucleus of the nucleus locus coeruleus and in the different parts of the raphe. In the white matter, low levels of binding were measured in the inferior cerebellar peduncle, the lateral and median lemnisci and the tractus solitarius. Conversely, moderate to high concentrations of somatostatin binding sites were measured in the median and superior cerebellar peduncles. The pyramis contained a very high density of recognition sites. A marked heterogeneity in the density of binding sites was observed within a few structures particularly in the medial accessory olivary of nucleus and the medial longitudinal fasciculus. Selective ligands were used to determine the pharmacological profile of the [Tyr11]somatostatin-14 binding sites in various brainstem regions. In the dorsal cochlear nucleus and the pyramis, all somatostatin binding sites belonged to the SSA subtype. Conversely, in the lateral paragigantocellular nucleus, all somatostatin binding sites belonged to the SSB subtype. The other regions studied contained various proportions of SSA and SSB subtypes. In conclusion, the present study shows that high concentrations of somatostatin receptors are present in many regions of the human fetus brainstem. These data support the concept that somatostatin could be involved in the maturation of brain structures.