The effects of intracisternally (i.c.) administered neurotensin (NT) on locomotor responses to scopolamine and caffeine, two psychomotor stimulants which do not depend on an intact mesolimbic dopamine (DA) system, were compared with the effects of the peptide on locomotion induced by d-amphetamine, which does depend on this DA system. Adult rats were injected intracisternally with 30 micrograms of neurotensin or vehicle. Immediately following these injections, the rats received intraperitoneal injections of either d-amphetamine (1, 2 or 3 mg/kg), scopolamine (0.25, 0.5, 1.0 or 2.0 mg/kg), caffeine (5, 15, 30 or 50 mg/kg) or the appropriate vehicle. After a 10 min recovery period, interruptions of photocells by ambulatory and non-ambulatory behavior were recorded every 30 min for 2 hr. Analyses of variance indicate that d-amphetamine and caffeine significantly elevated locomotor and non-locomotor activity at every dose tested. Scopolamine elevated locomotor activity at every dose and non-locomotor activity at 0.5, 1.0 and 2.0 mg/kg. Statistical analysis revealed that neurotensin significantly suppressed the locomotor response to 2 and 3 mg/kg of d-amphetamine but did not suppress the locomotor responses to any dose of scopolamine or caffeine or the non-locomotor responses to any of the three stimulants tested. Behavioral ratings of stereotyped responses indicated that neurotensin altered none of these responses to any stimulant tested. These findings are consistent with previous behavioral and biochemical data which indicate that neurotensin modulates the activity of the mesolimbic, but not nigroneostriatal, DA system and moreover, demonstrate that neurotensin does not simply induce a non-specific impairment of locomotor activity.