Acetic acid extracts of lyophilized samples of cerebrum, cerebellum, and various midbrain and hindbrain regions of bovine, simian and human brain cause darkening of the frog’s skin (melanotropic action) and release of free fatty acids from the rabbit's adipose tissue (lipolytic action). The melanotropic potencies of the regions of bovine brain vary according to the order: posterior pituitary gland 7900 / anterior pituitary gland 950 / hypothalamus 450 / choroid plexus 270 / pineal gland 200 / epithalamus 65 / area postrema 60 / subcommissural organ 30 / thalamus 20 / caudate nucleus 15 / cerebellum 10 / corpus callosum 2 / substantia nigra 2 / cerebral cortex 2 / medulla 2 / pyriform—amygdaloid 2 / midbrain 1 / septum pellucidum 1 / hippocampus 1 / pons 1. Lipolytic potencies of the regions vary in the same manner. The distribution of melanotropic and lipolytic activities in simian and human central nervous systems was similar to that in the bovine. Both biologic activities in extracts of all regions were abolished by exposure to trypsin. The active substances in bovine pineal gland, choroid plexus, cerebellum and cerbral cortex were purified by ion—exchange chromatography, gel—filtration and countercurrent distribution. Each of these tissues contained 2–6 melanotropic—lipolytic peptides, generally in molecular wt range 1000–3000. Melanotropic and lipolytic activities were detectable in a pool of cerebrospinal fluid from five monkeys and in all seven samples of human cerebrospinal fluid tested. Human cerebrospinal fluid contains (per ml) 30–350 units melanotropic activity and 0.05–10.7 units lipolytic activity. (Endocrinology92: 372, 1973)