Black widow spider venom (BWSV) elicited a prolonged tonic contraction of guinea-pig ileum which abolished the nicotine-induced contraction; however, the subsequent acetylcholine stimulation was found to be unchanged. These findings indicate a depletion of nerve terminal transmitters caused by BWSV without a disruption of the muscle contractile mechanism. Following the BWSV-induced contraction, the stimulation to 5-hydroxytryptamine (5-HT) was found to be abolished. This abolishment indicates a mediation of 5-HT-induced smooth muscle contraction in the nerve rather than the muscle.