1. Chronic (10 mg/kg, i.p., once daily for 14 days) but not acute (10 mg/kg, i.p., 24 hr) administration of imipramine resulted in a decrease in both the responsiveness and the sensitivity of the contractions of the isolated rat vas deferens elicited by field stimulation to GABA and (-)-baclofen. 2. In contrast, clonidine and isoproterenol effects were not altered by either treatment. 3. This study shows for the first time that GABA action in the peripheral nervous system is altered by chronic treatment with antidepressants, possibly by inducing changes in a postreceptor element.