The endothelin-1 (ET-1) plasma concentration was measured in dogs with spontaneous cardiac or respiratory diseases. Plasma samples were obtained from 76 healthy control dogs and 73 dogs, of which 58 were suffering from heart disease and 15 were suffering from respiratory disease. Dogs were evaluated using echocardiography, thoracic radiography, biochemical evaluation and a radioimmunoassay for ET-1. ET-1 plasma concentrations were significantly higher in dogs with spontaneous cardiac or respiratory diseases (mean [se] 5·3 [0·3] and 5·3 [0·6] pg/ml, respectively) than in healthy dogs (1·9 [0·1] pg/ml) (P<0·0001). ET-1 plasma concentrations increased with the class of heart failure (International Small Animal Cardiac Health Council classification) (P<0·0001) and with the severity of pulmonary disorders. ET-1 plasma concentrations were positively correlated with the extent of systolic pulmonary hypertension measured by Doppler echocardiography (P<0·05; r=0·75) and with the clinical outcome of dogs with respiratory disease. Evaluation of the ET-1 plasma concentration allowed differentiation between heart and respiratory disorders in dogs exhibiting clinical signs at exercise, but not in patients exhibiting clinical signs at rest.