Abstract Objective—To evaluate the effect of dilated cardiomyopathy (DCM) on activity of the reninangiotensin- aldosterone system (RAAS), the N-terminal fragment of proatrial natriuretic peptide (NTproANP), and thyroid hormone concentrations in dogs. Animals—15 dogs with clinical signs of DCM, 15 dogs without clinical signs of DCM, and 15 age-, breed-, and sex-matched control dogs. Procedure—Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs, and blood and urine samples were collected. Results—Plasma renin activity (PRA), plasma aldosterone concentration (PAC), urine aldosterone-to-creatinine ratio, and NT-proANP concentrations were significantly increased in dogs with clinical signs of DCM, compared with dogs without clinical signs and control dogs. Thyroid-stimulating hormone and total thyroxine concentrations did not differ significantly among groups; however, free thyroxine (FT₄) concentrations were significantly decreased in dogs with clinical signs of DCM, compared with control dogs and DCM-dogs without clinical signs. Concentrations of PRA, PAC, FT₄, and urine aldosterone-to-creatinine ratio were significantly correlated, whereas plasma concentrations of NT-proANP only correlated with FT₄ concentration. Conclusion and Clinical Relevance—In dogs with clinical signs of DCM, increased concentrations of components of the RAAS were associated with increased concentrations of NT-proANP. Analysis of the neurohormonal system may aid in identification of clinical stages of DCM for groups of dogs, but the range is too great and there are too many dogs that have neurohormonal concentrations within reference ranges to assess dogs on an individual basis. ( Am J Vet Res 2001;62:961–967)