Ten dogs with pituitary-dependent hyperadrenocorticism (PDH) received 2 mg/kg of L-Deprenyl once daily for 6 months. Monthly patient assessment consisted of evaluation of the owner's daily observation protocol, a standardized owner questionnaire, physical examination, CBC, biochemical profile, determination of the urine cortisol/creatinine ratio (UC/C), low-dose dexamethasone suppression (LDDS) test, corticotropin releasing hormone (CRH) test, and adrenal ultrasonography. At the beginning and the end of the study, an adrenocorticotropic hormone (ACTH) stimulation test and computed tomography also were performed. Two dogs developed neurologic signs and 2 dogs developed acute pancreatitis. An increase in activity, decrease in polyphagia, and decrease in panting were reported by 6, 4, and 2 owners, respectively. Seven owners believed that water intake decreased, but this was confirmed in only 3 dogs. Water intake increased in 2 dogs and remained unchanged in 5 dogs. The condition of the hair coat and skin improved in 2 dogs, worsened in 3, and remained unchanged in 5. Urine specific gravity, urine osmolality, ACTH test results, UC/C, and adrenal gland size did not change significantly throughout the study. In 4 of 8 dogs, LDDS was abnormal at the start of the study but normal at the end of the study, and in 2 dogs, the opposite occurred. Marked individual variation was noted in the CRH test, with a tendency for smaller increases in ACTH toward the end of the study. A marked increase in hypophyseal tumor size occured in 4 dogs. Treatment with L-Deprenyl resulted in improvement, deterioration, and stagnation of clinical signs in 2, 4, and 4 dogs, respectively. The results of this study indicate that L-Deprenyl cannot be recommended as the sole treatment for canine PDH.