Rats exposed to maternal antibodies against nerve growth factor (NGF) in utero and in milk have been used to investigate the developmental dependency of various substance P-containing neurons on NGF. Substance P and other peptides were measured by radioimmunoassays. The substance P content of sensory ganglia, spinal cord, and skin was depleted 40 to 60% in anti-NGF-treated rats. These results demonstrate the NGF dependence of substance P-containing neurons in sensory ganglia. Opiate binding in the spinal cord was not changed despite the large depletion in substance P: the Bmax and KD were the same in control and treated animals. The results suggest that opiate receptors may not be located presynaptically on substance P-containing primary afferents. Among the peripheral tissues which were assayed (ileum, submaxillary gland, retina, and adrenal), substance P decreased only in the adrenal, suggesting innervation by a NGF-dependent substance P-containing neuron. No changes were detected in the substance P content of nine different brain regions, in agreement with previous observations on the lack of effect of NGF on central neurons.