Neostigmine methylsulfate, a muscarinic drug, is frequently employed to reverse the paralytic effect of curare at the conclusion of surgical procedures. The experiments reported document the potent muscarinic effect of neostigmine on the large bowel, causing intraluminal colonic pressure to rise 15 times above base line. This is accompanied by severe spasm, associated with foreshortening and hypersegmentation of the bowel. The prior administration of atropine sulfate, an antimuscarinic drug, in the dose customarily employed during anesthesia, does not ameliorate or abolish the muscarinic effect of neostigmine on the canine colon. The muscarinic effects of neostigmine did not result in the disruption of an anastomosis fashioned in the canine colon.