BACKGROUND AND OBJECTIVES: Controversy exists regarding the role of endogenous ouabain in the pathogenesis of DOCA-salt induced hypertension. The purpose of this study was to investigate the role of endogenous ouabain in the development of hypertension in DOCA-salt rats. MATERIALS AND METHODS: The mean blood pressure and heart rate were recorded in 1, 2 and 4 week old control and DOCA-salt treated rats. The endogenous levels of ouabain in the plasma, hypothalamus, pituitary and adrenal glands of the 1, 2 and 4 week old control and DOCA-salt treated rats were also measured using a radioimmunoassay. RESULTS: The mean blood pressures in the 2 and 4 week old DOCA-salt treated rats were significantly higher than those of the controls. There was no significant change in the heart rate between the DOCA-salt treated and control groups. In the 4 week old DOCA-salt treated rats, the endogenous level of ouabain in the adrenal glands was higher than that in the control rats, but this was only weakly significant. The endogenous level of ouabain in the hypothalamus was significantly higher in the 1 week old DOCA-salt treated rats than in the control, but this significance disappeared in the 2 and 4 week old DOCA-salt treated rats. CONCLUSION: These results suggest that the endogenous level of ouabain contributes to the development and maintenance of high blood pressure in DOCA-salt rats. Further studies will be required to elucidate the relationship between the endogenous level of ouabain and DOCA-salt hypertension.