The antagonistic effect of various antidepressants and of alprazolam on muscarinic and histamine H1 receptors has been studied in the guinea-pig ileum, and those on histamine H2 receptors on rat uterus. All antidepressants act like competitive antagonists on muscarinic and histamine H1and H2 receptors. Alprazolam has shown competitive antagonism on muscarinic and histamine H1 receptors, and noncompetitive antagonism on histamine H2 receptors. Large differences in anticholinergic activity appear between the drugs studied, whereas all of them showed a higher histamine H1 receptor antagonistic activity. Most of the drugs studied showed a histamine H2 receptor antagonistic activity similar to that of cimetidine.