The effects of neurotensin were studied in the isolated mouse distal colon. This peptide had potent stimulatory effects which were of pre- or postjunctional origin according to the concentrations used. At low concentrations (10(-11)-10(-10) M) neurotensin induced neurogenic non-cholinergic contractions which seemed to result from the release of substance P (or substance P-like activity) by enteric excitatory nerves. At higher concentrations (10(-9)-10(-7) M) neurotensin elicited a biphasic effect consisting of transient relaxation rapidly followed by myogenic contraction. The bee venom toxin apamin inhibited the NT-induced relaxation while inhibition of prostaglandin synthesis by indomethacin abolished the contraction phase. All these responses were tightly related to the extracellular Ca2+ concentration. These properties of neurotensin point to a possible role for this peptide as a modulator of colonic motility.