Thyrotropin-releasing hormone (TRH) and cholecystokinin octapeptide (CCK) are endogenous neuropeptides known to inhibit intake of alcohol. Although both peptides are released by alcohol consumption and are hypothesized to satiate alcohol intake, their interaction has not been examined. We deprived ad-lib-fed male (n=6) and female (n=4) Wistar rats of water for 23 h and then gave them 30 min access to 5% w/v ethanol, followed by 30 min access to water. After adaptation to this schedule, rats were randomly assigned to receive intraperitoneal injections of either saline+saline, CCK (4 microg/kg)+saline, saline+TRH (10 mg/kg) or CCK+TRH immediately before alcohol access. Analyses of variance revealed a significant (P<.05) effect of CCK, and a significant interaction of CCK and TRH in control of ethanol consumption. CCK reliably reduced alcohol intake, and TRH blocked this satiation effect of CCK, increasing intake by 88.8% and 34.6% in males and females, respectively. TRH increased water intake in females, and CCK blocked this effect of TRH. Results indicate an infra-dose-additive interaction of CCK and TRH in satiation of alcohol intake, which may reflect a natural, endogenous neuropeptide interaction in the regulation of caloric intake.