Responses of isolated muscle strips from the rat and the dog internal anal sphincter (IAS) to drugs and electrical field stimulation (EFS) were investigated in vitro for the purpose of clarifying a manner of neural control of IAS. Also, responses of muscle strips from IAS of the patients with Hirschsprung's disease were compared with those of muscle strips from human control IAS. Muscle strips from the dog and human IAS as normal control showed contractions to norepinephrine (NE), which were abolished in the presence of phentolamine and relaxations to isoproterenol. EFS (less than 1 msec) induced relaxations of the muscle strips. These responses to EFS were not affected by either one of phentolamine, propranolol and atropine but were inhibited by tetrodotoxin. Muscle strips from IAS in Hirschsprung's disease contracted to both NE and EFS, the responses of which were abolished in the presence of phentolamine. But no relaxation to EFS of muscle strips from IAS in Hirschsprung's disease was observed. These findings revealed that normal IAS is pharmacologically innervated by alpha-adrenergic excitatory nerve, beta-adrenergic inhibitory nerve and non-adrenergic, non-cholinergic inhibitory nerve and suggested that IAS in Hirschsprung's disease is also affected by alpha-adrenergic excitatory nerve but inhibitory neural control is absent.