We evaluated the time course of changes in the relative contribution of arginine-vasopressin (AVP) and sympathetic nervous system (SNS) during the development of DOCA-salt hypertension in rats. Intravenous administrations of an AVP antagonist (d(CH2)5Tyr(Me) AVP; AVPA) and hexamethonium (C6) were given at 3 and 7 days, and 2 and 4 weeks after the initiation of treatment with DOCA-salt to conscious and unrestrained rats. Mean arterial pressure (MAP) was higher and heart rate (HR) tended to be rapid in the rats on DOCA-salt treatment for over 1 week, compared with those of the control groups. The hypotensive effect of AVPA in the DOCA-salt treated rats was gradually enhanced with the development of hypertension and was significantly greater than in the control rats, at all stages of hypertension, including the prehypertensive phase. The depressor response to intravenous C6 following AVPA also resulted in a gradual enhancement, with time, after DOCA treatment. This decrease in MAP was greater at the hypertensive stage than that in the control rats, although the response was not significantly different among three groups on the 3rd treatment day. It was concluded that the pressor systems AVP and SNS may contribute to the initiation and development as well as maintenance of DOCA-salt hypertension in rats.