The differential effects of the alpha-2 adrenergic agonist, clonidine, on blood pressure, renal sympathetic nerve activity (RSNA) and renal responses were investigated in conscious as well as anesthetized congestive heart failure (CHF) rats and normal control animals. After the stepwise increments of i.v. clonidine infusion (5, 15 and 30 micrograms/hr for 1 hr), mean arterial pressure gradually decreased in CHF, but increased significantly in the control animals at the higher doses. Urinary volume, sodium and potassium excretions were significantly higher in the normal control animals after the clonidine 30-micrograms/hr infusion compared with the CHF rats. There were almost immediate decreases in RSNA in both the CHF and control groups. Although the control animals reduced RSNA to about 5%, the CHF rats retained 36.5% of their respective control values after clonidine administration. Base-line plasma immunoreactive atrial natriuretic peptide were increased 7-fold in the CHF rats compared to controls. After clonidine, immunoreactive atrial natriuretic peptide increased more than 3-fold in the normal rats, whereas no changes were observed in the CHF group. Our data show that clonidine decreases RSNA in CHF and that the natriuretic and that diuretic effects of an alpha-2 receptor agonist are blunted in experimental CHF. Furthermore, the different mean arterial pressure response in the CHF and control groups at higher doses of clonidine may suggest down-regulation of the vascular alpha-2 adrenergic receptor in CHF.