Descending inhibition in the proximal and distal portions of rat colon was studied separately, in vitro. 2. In the proximal colon, localized distension with a small balloon caused three types of response (contraction; relaxation; relaxation, then contraction) of the circular muscle on the anal side of the distended region. 3. Distension caused descending relaxation of circular muscle in all segments of the proximal colon, although for this prostaglandin F2 alpha (PGF 2 alpha) was necessary in some segments to increase muscle tone. 4. Atropine and guanethidine did not inhibit this descending relaxation, but tetrodotoxin did. 5. Hexamethonium inhibited the descending relaxation in 14 of 17 preparations of proximal colon tested, but not in the others. 6. In the distal colon, distension consistently caused an increase in the tone of the circular muscles. Descending relaxation was observed only after development of higher tone. Atropine and guanethidine did not inhibit the relaxation, but tetrodotoxin did. 7. Hexamethonium did not inhibit the descending relaxation in most of the preparations of distal colon examined. 8. AF64A, an inhibitor of choline uptake, inhibited the response mediated by cholinergic neurons in vitro to electrical transmural stimulation of the longitudinal muscle of proximal colon. 9. Treatment of colonic preparations with AF64A in vitro resulted in inhibition of descending relaxation in those of proximal, but not those of distal, colon. 10. The participation of intrinsic cholinergic neurones in the descending neuronal pathway is strongly suggested by the results in the proximal colon, but less so in the distal colon. 11. The tone and spontaneous contractile activity of colonic circular muscles are discussed in relation to their neuronal control.
