I have used the peroxidase-antiperoxidase method for the light and electron microscopic localization of the enzymes used in the synthesis of monoamine neurotransmitters in brain. Immunocytochemistry has yielded considerable information on the ontogeny and synaptic interactions of the monoaminergic neurons and on the subcellular localization of the neurotransmitter-synthesizing enzymes and neuropeptides. In the proposed study, immunocytochemistry will be used to: (1) more fully characterize the development of enkephalin-, substance P-, and angiotensin II-containing neurons in fetal brain; and (2) examine the synaptic relationship between peptidergic and monoaminergic neurons in the nucleus tractus solitarius, spinal trigemnal complex and neostriatum of adult rat brain. The synaptic interactions will be investigated by combining the immunocytochemical localization of the three neuropeptides with the radioautographic localization of 3H-norepinephrine or 3H-serotonin. The information to be gained from these studies should provide an anatomical substrate for understanding how these peptides acting individually or in combination with each other or with specific monoaminergic neurons can elicit analgesic, cardiovascular and other physiological changes at least partially controlled by neuropeptides in the central nervous system (CNS).