Mechanical activity was recorded in muscle preparations isolated from different regions of dog and guinea pig stomach. Neurotensin (10−11 to 10−8 mol/liter) produced three types of responses in canine gastric muscle: a small activation of tone infundic strips and in longitudinal strips from corpus and antrum; a transient inhibition of the rhythmic activity in circular strips from corpus, antrum, and outer pylorus; and a strong activation in the strips from inner pylorus. In guinea pig gastric muscle strong tonic responses were observed in circular fundic muscle strips, whereas in all other preparations the responses were negligible. All these effects were insensitive to atropine, dimethpyrindene, and tetrodotoxin. The neurotensin effect on strips from guinea pig stomach was strongly reduced in the presence of indomethacin or cortisone and markedly potentiated in the presence of arachidonic acid or prostaglandin F2α. contrast, the excitatory effect of neurotensin on canine inner pylorus was potentiated during indomethacin treatment.