In DOCA-salt rats, the time course of synergistic interaction between osmolality and DOCA to produce hypertension is unknown. Therefore, in rats 2 wk after implantation of sc silicone pellets containing DOCA (65 mg) or no drug (Sham), we determined blood pressure (BP) and heart rate (HR) responses, using telemetric pressure transducers, during 2 wk of excess salt ingestion (1% NaCl in drinking water). BP was unaltered in Sham rats after increased salt, but in DOCA rats BP increased within 4 hr. The initial hypertension of 30-35 mmHg stabilized within 2 days, followed ~5 days later by a further increment of ~30 mmHg. HR first decreased during the dark phase; the second phase was linked to an abrupt increase in HR and BP variability, and decreased HR variability. Pressor responses to acute iv hypertonic saline infusion were doubled in DOCA-treated rats via vasopressin and non-vasopressin mechanisms. Only in DOCA-treated rats, portal vein hypertonic saline infusion increased BP, which was prevented by V1 vasopressin blockade. After 2 wk of DOCA-salt, oral ingestion of water rapidly decreased BP. Intraportal infusion of water did not lower BP in DOCA-salt rats, suggesting that hepatic osmoreceptors were not involved. In summary, the hypertension of DOCA-treated rats consuming excess salt exhibits multiple phases and can be rapidly reversed. Hypertonicity-induced vasopressin and non-vasopressin pressor mechanisms, augmented by DOCA, and hepatic osmoreceptors may contribute to the initial developmental phase. With time, combined DOCA-salt induces marked changes in the regulation of the autonomic nervous system, which may favor hypertension development.