The effect of angiotensin II (ANG II) on the secretion of angiotensinogen was studied in isolated rat hepatocytes, obtained by the collagenase perfusion technique and Percoll-density gradient centrifugation, and in the isolated perfused rat liver. In isolated hepatocytes, steady state concentrations of about 1, 10 or 100 nM of ANG II during 90 min of preincubation resulted in a 5, 27 and 33% increase of angiotensinogen secreted during a subsequent 3 hour incubation period. Secretion rates during the last hour of incubation were increased by about 70% by the two higher ANG II concentrations, as compared to controls. Hydrocortisone also induced an increased secretion of angiotensinogen in hepatocytes. The effect of ANG II was prevented by saralasin, a competitive ANG II-antagonist and by actinomycin D. ANG II had no effect of the rate of albumin secretion and of total protein secretion. In the isolated perfused liver, ANG II induced a similar increase of angiotensinogen secretion, without affecting albumin and total protein secretion rates. These observations are consistent with the view that ANG II is participating in a feed back stimulation system of angiotensinogen synthesis and secretion in vivo.