A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as PhyUomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKE-VGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to Al adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans. We here identify the frog used by the Peruvian Matses and Brazilian Mayoruna Indians as Phyllomedusa bicolor (Boddaert), a large green hylid that inhabits lowland rain forest throughout much of the Amazon basin and the Guayanan region (Fig. 1 Upper). Skin extracts from this species have been previously studied and are known to contain a variety of vasoactive peptides (4). These include high levels of phyllocaerulein, phyllokinin, and phyllomedusin and moderate levels of sauvagine. Small amounts of deltorphins, a class of opioid agonists selective for 8 receptors, also are present (5). We initially felt it unlikely that either the vasoactive peptides or the small amounts of deltorphins would account for effects on humans attributed to secretions from P. bicolor. Therefore, an examination was initiated of the effects of extracts of dried secretion from a Mayoruna frog stick.EXPERIMENTAL PROCEDURES AND RESULTS Extraction and Behavioral Effects. A stick holding dried skin secretion from P. bicolor was acquired by K.M. at the Rio Lobo site in western Brazil. The Rio Lobo stick was scraped to provide 400 mg of dried frog secretion, which was triturated first with 6 ml of methanol to yield a pale yellow methanol extract and then with 6 ml of water to yield a pale yellow aqueous extract. Extracts were stored at -20'C. Subcutaneous injection into mice of methanol and aqueous extracts in doses equivalent to 0.1-6 mg of dried secretion resulted in a dose-dependent reduction in spontaneous locomotor activity. At higher doses mice were completely inactive for several hours, although when touched they would respond briefly and then reassume a lethargic state. The aqueous extract produced a less active state at a threshold dose equivalent to 0.1 mg of dried secretion, whereas the methanol extract required a dose of 0. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.