The tridecapeptide neurotensin (NT) induces a variety of behavioral changes in animals. The present study characterizes the behavioral hypoactivity observed after intracerebroventricular (ICV) injection in mice. At doses higher than 25 ng, NT induced a reduction of general motor activity and increases in immobility which lasted for about one hour. The NT-related amphibian skin peptide xenopsin was about 70-fold more potent than NT itself. After repeated NT-injections, tolerance developed within 2-4 days and disappeared within 2-4 days after cessation of the treatment. The motor hypoactivity induced by NT was not attenuated by pretreatment with naloxone (5 mg/kg, SC). Furthermore, amphetamine-induced locomotor activity was not blocked by NT or xenopsin. These results suggest that the NT-effect is not mediated by a stimulation of opioid mechanisms or attenuation of dopamine-mediated events.