Peptides of the neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) families have been reported to modulate, in vivo, sigma receptor systems in the mouse and rat hippocampal formation. In an attempt to determine if these interactions were specific to the hippocampal formation, quantitative ex vivo autoradiography was used with (+)(-)[3H]SKF 10,047 as sigma ligand after i.c.v. injections of various NPY and CGRP peptides. High levels of specific (+)(-)[3H]SKF 10,047 labeling were concentrated in various cranial nerve nuclei, whereas lower but still significant amounts of labeling were seen in the cortex, hippocampus, various hypothalamic nuclei, red nucleus, substantia nigra, central gray and cerebellum. In all brain areas enriched with specific (+)(-)[3H]SKF 10,047/sigma labeling, the Y1 receptor subtype agonist [Leu31Pro34]-NPY, as well as peptide YY and rCGRP beta, inhibited, to a rather similar extent, (+)(-)[3H]SKF 10,047 labeling. The Y2 receptor agonist NPY13-36 had no effect in any of the regions studied. These results extend findings obtained in the hippocampal formation and demonstrate the existence of in vivo modulatory effects of NPY and CGRP-related peptides on sigma sites throughout the mouse brain.