Cimetidine produced dose-dependent contractions in isolated guinea pig ileum and these responses were not blocked by mepyramine the H1-receptor antagonist. 2. Atropine competitively inhibited the cimetidine-induced contractions in the guinea pig ileum. 3. Cimetidine-induced responses were potentiated in the presence of eserine. Magnesium ions non-competitively inhibited the contractions due to cimetidine. Our findings suggest that cimetidine excites the guinea pig ileum through muscarinic receptors by releasing acetylcholine.