The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8–13) [NT(8–13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8–13), (N-methyl-Arg),Lys,Pro,l-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, l-neo-tryptophan and exhibits high affinity for the rat and human neurotensin receptor, subtype 1. After intraperitoneal (i.p.) injection (1 mg/kg), NT69L induced hypothermia of >5°C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic.