The ontogeny of somatostatin binding sites was studied in 16 respiratory nuclei of the human brainstem, from 19 postconceptional weeks to 6 months postnatal, by quantitative autoradiography using [(125)I-Tyr0,DTrp8]S14 as a radioligand. In the early gestational stages (19-21 postconceptional weeks), moderate to high concentrations of [(125)I-Tyr0,DTrp8]S14 binding sites were found in all nuclei, the highest density being measured in the locus coeruleus. From 19 weeks of fetal life to 6 months postnatal, a decrease in the density of labeling was observed in all nuclei. The most dramatic reduction in site density (80-90%) was found in the ventral part of the nucleus medullae oblongata lateralis and in the nucleus paragigantocellularis lateralis. A 70-80% decrease was detected in the dorsal part of the nucleus tractus solitarius, the nucleus nervi hypoglossi, the ventral part of the nucleus medullae oblongatae centralis, the nucleus ambiguus, the nucleus paragigantocellularis dorsalis, and the nucleus gigantocellularis, and a 60-70% decrease in the nucleus parabrachialis medialis, the ventrolateral and ventromedial parts of the nucleus tractus solitarius, and the nucleus praepositus hypoglossi. A 50-60% decrease was observed in the caudal part of the nucleus tractus solitarius, the nucleus dorsalis motorius nervi vagi, and the nucleus parabrachialis lateralis, whereas in the nucleus locus coeruleus, the concentration of recognition sites decreased by only 30%. The profiles of the decrease in site density differed in the various structures. In the majority of the nuclei, a gradual diminution of binding density was observed either throughout the developmental period studied or mainly during fetal life. Conversely, in two nuclei, i.e., the nucleus parabrachialis lateralis and the locus coeruleus, an abrupt decrease occurred around birth. The differential decrease in the density of somatostatin binding sites observed in respiratory nuclei during development, together with the observation that microinjection of somatostatin in some of these nuclei causes ventilatory depression and apnea, strongly suggests that the somatostatinergic systems of the human brainstem are involved in the maturation of the respiratory control.