Six healthy male subjects were randomly given nortriptyline (NT) (25 and 50 mg) and placebo in a double‐blind, crossover study. An NT dose of 50 mg (but not 25 mg) clearly reduced saliva flow (P<0.05) and was therefore used for comparison with the major and active metabolite of NT, E‐10‐hydroxynortriptyline (E‐10‐OH‐NT). Equimolar doses of both compounds (and placebo) were randomly given to eight healthy male subjects in another double‐blind, crossover study aimed to assess the reduction of saliva flow. NT significantly depressed saliva flow compared with both placebo (P<0.01) and E‐10‐OH‐NT (P<0.05). By contrast, there was no difference between E‐10‐OH‐NT and placebo. This study confirms previous indications that the anticholinergic effect of E‐10‐OH‐NT is considerably less than that of the parent drug NT.Clinical Pharmacology and Therapeutics(1987)41,