Rotating disk electrode voltammetry at glassy carbon electrodes and ultraviolet/visible spectroscopy were used to demonstrate that dopamine binds to neurotensin with a dissociation constant of 7.5 x 10(-8). By measuring the binding constants of various neurotensin analogs, it was found that the -Arg8-Arg9-portion of the neurotensin sequence is critical for binding dopamine. Neurotensin also formed a complex with 4-ethylcatechol, 4-methylcatechol, 3-methoxytyramine, and norepinephrine. Although changes in the side chain did not alter the binding constant, methoxylation of the catechol moiety significantly increased the dissociation constant. These data along with additional studies of dopamine interactions with arginine derivatives suggest that the guanidino groups of arginine and the catechol hydroxyls of dopamine are responsible for mediating the observed binding. It is hypothesized that the capacity of neurotensin to bind directly to dopamine may be partly responsible for its previously observed antagonism of dopamine-induced locomotor activity.