We examined the ability of antidepressant drugs belonging to different classes to interfere with human polymorphonuclear cell migration in vitro. 1. The tricyclic antidepressant drugs chlorimipramine and nortriptyline were able to block, in a dose related fashion both spontaneous and formyl-methionyl-leucyl-phenylalanine stimulated migration. This effect was already evident at very low concentrations (10(-7)M). 2. The atypical non-tricyclic antidepressant drugs fluoxetine and fluvoxamine did not affect polymorphonuclear cell mobility. 3. The ability of antidepressant drugs to interfere with polymorphonuclear cell physiology seems to depend on their chemical structures.