O,O,S-Trimethylphosphorothioate (OOS-TMP), an impurity present in various organophosphorus insecticides, has previously been shown to induce hypophagia. The major goal of this study was to investigate its mechanism of action. Both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injection transiently induced hypophagia at a dose of 5 mg/kg within 6 h, without causing lung injury. Hypophagia was accompanied by up-regulation of corticotropin releasing factor (CRF) (2.92 +/- 0.45 vs. 1.7 +/- 0.5, at 2 h after i.c.v., 3.40 +/- 1.38 vs. 1.76 +/- 0.41 at 6 h after i.p., P < 0.05) in the hypothalamus. After i.c.v. injection, hypophagia recovered by 6 h after dosing. At doses higher than 5 mg/kg, i.c.v. injection induced continuous hypophagia from 20 min to 72 It after dosing, accompanied by hypothermia and lung injury. OOS-TMP was considered to induce hypophagia through enhancing expression of CRF. (C) 2007 Elsevier Inc. All rights reserved.