Proglumide has been reported to antagonize sulfated cholecystokinin octapeptide (CCK-8) in peripheral tissue and in neurophysiological single unit preparations. The present studies attempt to extend this reported antagonism to several actions of CCK-8 in mice in vivo. For comparison with proglumide, the antagonist activity of naloxone against CCK-8 has also been evaluated. Proglumide (150 mg/kg) antagonizes hot plate latency elevations produced by a moderate (0.17 mg/kg s.c.) dose of CCK-8, but not that by a higher (1.0 mg/kg) dose. The effects of intracerebroventricularly (i.c.v.) administered CCK-8 (0.3 micrograms) are also blocked by proglumide i.p. or i.c.v. Naloxone (0.5 mg/kg s.c.) significantly antagonizes the elevated hot plate latencies induced by CCK-8 i.c.v. (3.0 micrograms) and s.c. (3.0 mg/kg). Proglumide antagonizes the motor activity suppressant effects of CCK-8, but only at a high proglumide dose (150 mg/kg i.p.) and low CCK-8 doses. Naloxone (3.0 mg/kg) is not effective against CCK-8 in motor activity. The hypothermia induced by CCK-8 cannot be antagonized either by proglumide at doses up to 150 mg/kg i.p. or by naloxone at doses up to 3.0 mg/kg s.c. In vivo, proglumide may be considered as a weak antagonist of CCK-8 and the possibility exists that various actions of CCK-8 may be differentiated by their relative responsiveness to proglumide-induced antagonism.