This study included 120 patients with major depressive disorder, divided into three groups: Group I included 60 Ss received tricyclic antidepressants (half on amitriptyline and the other half on imipramine); Group II included 30 Ss received tetracyclic antidepressant maprotilin; and Group III included 30 Ss received monoamine oxidase inhibitor tranylcypromine. To evaluate the anticholinergic effects, all Ss were submitted to the following (before and after 6 days of using antidepressants): (a) estimation of volume of salivary secretion; (b) estimation of concentration of salivary secretion; and (c) estimation of serum cholinesterase enzyme. The results revealed the following: the four drugs have decreasing effect on salivary juice volume which could be used as indicator for the severity of anticholinergic activity; tricyclics have more significant lowering of salivary volume than the other two; the anticholinergic effects of antidepressants are not only due to the relative affinity of these drugs for muscarine receptors as it was believed before, but it could be also attributed to the increase in serum cholinesterase enzyme. The increased concentrations of salivary amylase and bicarbonate could be ascribed to the increase in norepinephrine which accompanies using these drugs.